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nord_1285_5
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Diagnosis of Weaver Syndrome
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The growth changes seen with WS are broad and could be caused by many overgrowth syndromes. Genetic testing can diagnose WS and finding a harmful change in the EZH2 gene confirms WS. Because the symptoms of WS are not specific, genetic testing may include many genes that cause overgrowth syndromes (gene panel).Clinical Testing & WorkupPeople with WS need many clinical assessments after diagnosis. A neurology assessment can identify delays and rigid muscles. Psychologists can identify behavior issues. Examinations by specialists are needed to look for problems with the heart, hands or feet. Results from these evaluations will help guide what other testing should be done.
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Diagnosis of Weaver Syndrome. The growth changes seen with WS are broad and could be caused by many overgrowth syndromes. Genetic testing can diagnose WS and finding a harmful change in the EZH2 gene confirms WS. Because the symptoms of WS are not specific, genetic testing may include many genes that cause overgrowth syndromes (gene panel).Clinical Testing & WorkupPeople with WS need many clinical assessments after diagnosis. A neurology assessment can identify delays and rigid muscles. Psychologists can identify behavior issues. Examinations by specialists are needed to look for problems with the heart, hands or feet. Results from these evaluations will help guide what other testing should be done.
| 1,285 |
Weaver Syndrome
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nord_1285_6
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Therapies of Weaver Syndrome
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Treatment of WS involves management of symptoms and is supportive. Physical therapy may be helpful for rigid muscles, foot differences and bent fingers or toes. Surgery may be needed to correct problems with the fingers, toes or feet. Therapies or individual education plans (IEPs) may be helpful for children with WS.Genetic counseling is recommended for patients and their families.
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Therapies of Weaver Syndrome. Treatment of WS involves management of symptoms and is supportive. Physical therapy may be helpful for rigid muscles, foot differences and bent fingers or toes. Surgery may be needed to correct problems with the fingers, toes or feet. Therapies or individual education plans (IEPs) may be helpful for children with WS.Genetic counseling is recommended for patients and their families.
| 1,285 |
Weaver Syndrome
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nord_1286_0
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Overview of Weil Syndrome
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Weil syndrome, a rare infectious disorder, is a severe form of the bacterial infection caused by Leptospira bacteria known as leptospirosis. Weil syndrome is characterized by dysfunction of the kidneys and liver, abnormal enlargement of the liver (hepatomegaly), persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), and/or alterations in consciousness. In most cases, Weil syndrome occurs among individuals who are exposed to affected animals.
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Overview of Weil Syndrome. Weil syndrome, a rare infectious disorder, is a severe form of the bacterial infection caused by Leptospira bacteria known as leptospirosis. Weil syndrome is characterized by dysfunction of the kidneys and liver, abnormal enlargement of the liver (hepatomegaly), persistent yellowing of the skin, mucous membranes, and whites of the eyes (jaundice), and/or alterations in consciousness. In most cases, Weil syndrome occurs among individuals who are exposed to affected animals.
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Weil Syndrome
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nord_1286_1
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Symptoms of Weil Syndrome
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Symptoms of Weil syndrome usually start abruptly, with headache, disturbances in consciousness, pain in muscles and abdomen, a stiff neck, lack of appetite (anorexia), chills, nausea, vomiting, and fever. Prostration, coughing, expectoration of blood-stained sputum (hemoptysis), and nosebleed (epistaxis) may also occur. Yellowing of the skin (jaundice), bleeding in muscles, gastrointestinal tract, and visceral organs may be widespread. Small purplish-red spots (petechiae) may appear, caused by hemorrhages in the skin. Enlarged lymph nodes, and continued fever may occur for several days. Respiratory distress syndrome which includes great difficulty breathing and dangerously low levels of oxygen in the blood (hypoxemia) may sometimes develop in Weil syndrome.Signs of liver and kidney dysfunction usually appear from the 3rd to the 6th day. Kidney abnormalities may include the appearance of protein (proteinuria), pus (pyuria), or blood in the urine (hematuria), and an excess of urea in the blood (azotemia). The kidney is often enlarged, and its capsule is tense. Bleeding in many places throughout the body may occur due to injury of tiny blood vessels (capillaries). A low number of blood platelets (thrombocytopenia) may also occur. Damage to the liver is usually minimal and complete healing almost always occurs. Fever usually abates on the 7th day, but it may be recurrent for weeks. After age 50 the prognosis for Weil syndrome is less optimistic than for younger people.
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Symptoms of Weil Syndrome. Symptoms of Weil syndrome usually start abruptly, with headache, disturbances in consciousness, pain in muscles and abdomen, a stiff neck, lack of appetite (anorexia), chills, nausea, vomiting, and fever. Prostration, coughing, expectoration of blood-stained sputum (hemoptysis), and nosebleed (epistaxis) may also occur. Yellowing of the skin (jaundice), bleeding in muscles, gastrointestinal tract, and visceral organs may be widespread. Small purplish-red spots (petechiae) may appear, caused by hemorrhages in the skin. Enlarged lymph nodes, and continued fever may occur for several days. Respiratory distress syndrome which includes great difficulty breathing and dangerously low levels of oxygen in the blood (hypoxemia) may sometimes develop in Weil syndrome.Signs of liver and kidney dysfunction usually appear from the 3rd to the 6th day. Kidney abnormalities may include the appearance of protein (proteinuria), pus (pyuria), or blood in the urine (hematuria), and an excess of urea in the blood (azotemia). The kidney is often enlarged, and its capsule is tense. Bleeding in many places throughout the body may occur due to injury of tiny blood vessels (capillaries). A low number of blood platelets (thrombocytopenia) may also occur. Damage to the liver is usually minimal and complete healing almost always occurs. Fever usually abates on the 7th day, but it may be recurrent for weeks. After age 50 the prognosis for Weil syndrome is less optimistic than for younger people.
| 1,286 |
Weil Syndrome
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nord_1286_2
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Causes of Weil Syndrome
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Weil syndrome is caused by an infection from the bacteria Leptospira icterohemorrhagiae or other related types of this bacteria (such as L canicola, or L pomona). The infection is usually transferred to humans through urine or tissue of an infected domestic or wild animal. The infection enters through a skin abrasion or the mucous membranes.
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Causes of Weil Syndrome. Weil syndrome is caused by an infection from the bacteria Leptospira icterohemorrhagiae or other related types of this bacteria (such as L canicola, or L pomona). The infection is usually transferred to humans through urine or tissue of an infected domestic or wild animal. The infection enters through a skin abrasion or the mucous membranes.
| 1,286 |
Weil Syndrome
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nord_1286_3
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Affects of Weil Syndrome
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Weil syndrome may occur in people of all ages. At least 75% of persons infected with this disorder are male. It can be an occupational disorder striking farmers, veterinarians, or sewer and abattoir workers, but most patients are exposed incidentally during recreational activities.
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Affects of Weil Syndrome. Weil syndrome may occur in people of all ages. At least 75% of persons infected with this disorder are male. It can be an occupational disorder striking farmers, veterinarians, or sewer and abattoir workers, but most patients are exposed incidentally during recreational activities.
| 1,286 |
Weil Syndrome
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nord_1286_4
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Related disorders of Weil Syndrome
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Many types of bacterial infections may affect the liver, kidneys and respiratory organs, causing symptoms similar to those of Weil syndrome.Leptospirosis is an inclusive term for all bacterial infections caused by any Leptospira bacteria, regardless of the type. (For more information, choose “Leptospirosis” as your search term in the Rare Disease Database.)Meningitis is an infection of the membrane lining the skull or the spinal cavity (meninges) by either bacteria or viruses.
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Related disorders of Weil Syndrome. Many types of bacterial infections may affect the liver, kidneys and respiratory organs, causing symptoms similar to those of Weil syndrome.Leptospirosis is an inclusive term for all bacterial infections caused by any Leptospira bacteria, regardless of the type. (For more information, choose “Leptospirosis” as your search term in the Rare Disease Database.)Meningitis is an infection of the membrane lining the skull or the spinal cavity (meninges) by either bacteria or viruses.
| 1,286 |
Weil Syndrome
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nord_1286_5
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Diagnosis of Weil Syndrome
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The results of various laboratory tests, including blood and urine tests, assist in the diagnosis.
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Diagnosis of Weil Syndrome. The results of various laboratory tests, including blood and urine tests, assist in the diagnosis.
| 1,286 |
Weil Syndrome
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nord_1286_6
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Therapies of Weil Syndrome
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TreatmentIf begun in the first three or four days after the onset of symptoms, the intravenous administration of antibiotics may be effective. Peritoneal dialysis in combination with antibiotics has been used successfully in some patients.
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Therapies of Weil Syndrome. TreatmentIf begun in the first three or four days after the onset of symptoms, the intravenous administration of antibiotics may be effective. Peritoneal dialysis in combination with antibiotics has been used successfully in some patients.
| 1,286 |
Weil Syndrome
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nord_1287_0
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Overview of Weill Marchesani Syndrome
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Weill Marchesani syndrome is a rare genetic disorder of connective tissue characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. The eye (ocular) abnormalities can include small round lenses (microspherophakia), abnormal position of the lens (ectopia lentis) nearsightedness (myopia) resulting from the abnormal shape of the eye and lens and eye disease that damages the optic nerve (glaucoma) that can lead to blindness. Heart defects are present in some affected individuals. Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.
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Overview of Weill Marchesani Syndrome. Weill Marchesani syndrome is a rare genetic disorder of connective tissue characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. The eye (ocular) abnormalities can include small round lenses (microspherophakia), abnormal position of the lens (ectopia lentis) nearsightedness (myopia) resulting from the abnormal shape of the eye and lens and eye disease that damages the optic nerve (glaucoma) that can lead to blindness. Heart defects are present in some affected individuals. Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.
| 1,287 |
Weill Marchesani Syndrome
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nord_1287_1
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Symptoms of Weill Marchesani Syndrome
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The symptoms and findings associated with Weill-Marchesani syndrome vary from person to person. Weill-Marchesani syndrome is characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. Many affected individuals have additional craniofacial abnormalities including a narrow roof of the mouth (palate); a small, underdeveloped upper jaw (maxillary hypoplasia); and/or malformation and misalignment of certain teeth.Affected individuals often have microspherophakia (a smaller and rounder lens than normal) with partial or complete absence of certain fibers (zonula ciliaris) that normally help to hold the lenses in place. As a result, some individuals with the disorder may be prone to developing progressive dislocation of the lenses (ectopia lentis) or may have the condition at birth (congenital ectopia lentis). Ectopia lentis may be characterized by shifting or tilting (i.e., partial displacement or subluxation) or complete dislocation (luxation) of the lenses, resulting in blurring of vision, double vision (diplopia), and/or quivering movements of the colored regions of the eyes (iridodonesis). Additional ocular abnormalities may also be associated with Weill-Marchesani syndrome. These may include loss of transparency of the lenses of the eyes (cataracts); abnormal shallowness of the chambers (i.e., anterior chambers) in front of the colored regions of the eye (irides) that contain the thin, watery fluid known as aqueous humor; and/or secondary glaucoma. Glaucoma is characterized by abnormally increased pressure of the fluid of the eye. Individuals with Weill-Marchesani syndrome may have varying degrees of visual impairment, including reduced clearness and clarity of vision (acuity), marked nearsightedness (myopia), or blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.Short stature is usually present and digits may be short. In addition, some individuals may develop progressive stiffness of certain joints, particularly those of the hands.Heart abnormalities have been reported occasionally and include a defect where an opening remains between the aorta and the pulmonary artery (patent ductus arteriosis), a narrowed pulmonary valve (pulmonary stenosis) and recently thoracic aortic aneurysm and cervical artery dissection.
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Symptoms of Weill Marchesani Syndrome. The symptoms and findings associated with Weill-Marchesani syndrome vary from person to person. Weill-Marchesani syndrome is characterized by abnormalities of the lens of the eye, short stature, an unusually short, broad head (brachycephaly) and joint stiffness. Many affected individuals have additional craniofacial abnormalities including a narrow roof of the mouth (palate); a small, underdeveloped upper jaw (maxillary hypoplasia); and/or malformation and misalignment of certain teeth.Affected individuals often have microspherophakia (a smaller and rounder lens than normal) with partial or complete absence of certain fibers (zonula ciliaris) that normally help to hold the lenses in place. As a result, some individuals with the disorder may be prone to developing progressive dislocation of the lenses (ectopia lentis) or may have the condition at birth (congenital ectopia lentis). Ectopia lentis may be characterized by shifting or tilting (i.e., partial displacement or subluxation) or complete dislocation (luxation) of the lenses, resulting in blurring of vision, double vision (diplopia), and/or quivering movements of the colored regions of the eyes (iridodonesis). Additional ocular abnormalities may also be associated with Weill-Marchesani syndrome. These may include loss of transparency of the lenses of the eyes (cataracts); abnormal shallowness of the chambers (i.e., anterior chambers) in front of the colored regions of the eye (irides) that contain the thin, watery fluid known as aqueous humor; and/or secondary glaucoma. Glaucoma is characterized by abnormally increased pressure of the fluid of the eye. Individuals with Weill-Marchesani syndrome may have varying degrees of visual impairment, including reduced clearness and clarity of vision (acuity), marked nearsightedness (myopia), or blindness. The degree of visual impairment depends upon the severity and/or combination of eye abnormalities present.Short stature is usually present and digits may be short. In addition, some individuals may develop progressive stiffness of certain joints, particularly those of the hands.Heart abnormalities have been reported occasionally and include a defect where an opening remains between the aorta and the pulmonary artery (patent ductus arteriosis), a narrowed pulmonary valve (pulmonary stenosis) and recently thoracic aortic aneurysm and cervical artery dissection.
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Weill Marchesani Syndrome
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nord_1287_2
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Causes of Weill Marchesani Syndrome
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Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females. The ADAMTS10 gene has been found to be associated with autosomal recessive Weill Marchesani syndrome.Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.The FBN1 and LTBP2 genes have been found to be associated with autosomal dominant Weill Marchesani syndrome in one family each.
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Causes of Weill Marchesani Syndrome. Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females. The ADAMTS10 gene has been found to be associated with autosomal recessive Weill Marchesani syndrome.Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular disease. The abnormal gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the abnormal gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.The FBN1 and LTBP2 genes have been found to be associated with autosomal dominant Weill Marchesani syndrome in one family each.
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Weill Marchesani Syndrome
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nord_1287_3
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Affects of Weill Marchesani Syndrome
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Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.
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Affects of Weill Marchesani Syndrome. Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.
| 1,287 |
Weill Marchesani Syndrome
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nord_1287_4
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Related disorders of Weill Marchesani Syndrome
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Symptoms of the following disorders may be similar to those of Weill-Marchesani syndrome. Comparisons may be useful for a differential diagnosis:Simple ectopia lentis is an isolated eye (ocular) abnormality characterized by shifting or tilting (i.e., partial displacement) or complete displacement of the lens of the eye. In such cases, the condition may be present at birth or develop later during life. Simple ectopia lentis is usually inherited in an autosomal dominant pattern. In addition to Weill-Marchesani syndrome and simple ectopia lentis, abnormal position of the lens (ectopia lentis) may also occur in association with other underlying genetic disorders, including Marfan syndrome, a connective tissue disorder, and homocystinuria, a metabolic disorder. (For further information on these disorders, choose “Marfan” or “homocystinuria” as your search terms in the Rare Disease Database.)Additional disorders may be characterized by ectopia lentis, additional ocular abnormalities, short stature, skeletal malformations, and/or other symptoms and findings similar to those potentially associated with Weill-Marchesani syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Weill Marchesani Syndrome. Symptoms of the following disorders may be similar to those of Weill-Marchesani syndrome. Comparisons may be useful for a differential diagnosis:Simple ectopia lentis is an isolated eye (ocular) abnormality characterized by shifting or tilting (i.e., partial displacement) or complete displacement of the lens of the eye. In such cases, the condition may be present at birth or develop later during life. Simple ectopia lentis is usually inherited in an autosomal dominant pattern. In addition to Weill-Marchesani syndrome and simple ectopia lentis, abnormal position of the lens (ectopia lentis) may also occur in association with other underlying genetic disorders, including Marfan syndrome, a connective tissue disorder, and homocystinuria, a metabolic disorder. (For further information on these disorders, choose “Marfan” or “homocystinuria” as your search terms in the Rare Disease Database.)Additional disorders may be characterized by ectopia lentis, additional ocular abnormalities, short stature, skeletal malformations, and/or other symptoms and findings similar to those potentially associated with Weill-Marchesani syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
| 1,287 |
Weill Marchesani Syndrome
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nord_1287_5
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Diagnosis of Weill Marchesani Syndrome
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The diagnosis of Weill-Marchesani syndrome may be made based upon a thorough clinical examination, a complete patient and family history, identification of characteristic physical findings, and a variety of specialized tests. These typically include ocular examinations, such as the use of an instrument to view the inside of the eyes (ophthalmoscopy); techniques to measure pressure within the eyes (e.g., tonometry); visual field testing; and/or other ocular techniques. In addition, advanced imaging techniques (e.g., computed tomography [CT] scanning or magnetic resonance imaging [MRI]) or other diagnostic tests may be conducted to detect and characterize skeletal or other abnormalities that may be associated with the disorder. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. During MRI, a magnetic field and radio waves create detailed cross-sectional images of certain organs and tissues.Physical findings cannot differentiate between autosomal recessive and autosomal dominant Weill Marchesani syndrome. Molecular genetic testing for the ADAMTS10 gene is available to confirm the diagnosis of the autosomal recessive type.
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Diagnosis of Weill Marchesani Syndrome. The diagnosis of Weill-Marchesani syndrome may be made based upon a thorough clinical examination, a complete patient and family history, identification of characteristic physical findings, and a variety of specialized tests. These typically include ocular examinations, such as the use of an instrument to view the inside of the eyes (ophthalmoscopy); techniques to measure pressure within the eyes (e.g., tonometry); visual field testing; and/or other ocular techniques. In addition, advanced imaging techniques (e.g., computed tomography [CT] scanning or magnetic resonance imaging [MRI]) or other diagnostic tests may be conducted to detect and characterize skeletal or other abnormalities that may be associated with the disorder. During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. During MRI, a magnetic field and radio waves create detailed cross-sectional images of certain organs and tissues.Physical findings cannot differentiate between autosomal recessive and autosomal dominant Weill Marchesani syndrome. Molecular genetic testing for the ADAMTS10 gene is available to confirm the diagnosis of the autosomal recessive type.
| 1,287 |
Weill Marchesani Syndrome
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nord_1287_6
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Therapies of Weill Marchesani Syndrome
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TreatmentThe treatment of Weill-Marchesani 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, such as pediatricians; eye specialists (e.g., ophthalmologists and optometrists); physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and physicians who diagnose heart abnormalities (cardiologists).Specific therapies for Weill-Marchesani syndrome are symptomatic and supportive. Experts indicate that early diagnosis of ocular abnormalities may be important in helping to ensure optimal visual development. In some cases, corrective glasses, other visual aids, and/or surgery may be recommended to help improve vision. In addition, for those with increasing fluid pressure in the eyes or glaucoma, treatment may include measures to help control pressure within the eyes (intraocular pressure), such as therapy with medicated eye drops; laser therapy to create a hole in the colored region of the eye (laser iridectomy) or surgical removal of part of the iris (iridotomy); removal of the lens; and/or other techniques.Experts indicate that stimulating contraction (miosis) or dilation (mydriasis) of the pupils may induce glaucoma in some affected individuals. Therefore, therapy with medications that cause the pupils to contract must be avoided (i.e., are contraindicated) and dilation of the eyes should be done with extreme care.Affected individuals should notify their physician of this diagnosis prior to receiving anesthesia. Joint stiffness and craniofacial abnormalities can influence airway management.Genetic counseling is recommended for individuals with Weill-Marchesani syndrome and their families. Other treatment for this disorder is symptomatic and supportive.
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Therapies of Weill Marchesani Syndrome. TreatmentThe treatment of Weill-Marchesani 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, such as pediatricians; eye specialists (e.g., ophthalmologists and optometrists); physicians who diagnose and treat disorders of the skeleton, joints, muscles, and related tissues (orthopedists); and physicians who diagnose heart abnormalities (cardiologists).Specific therapies for Weill-Marchesani syndrome are symptomatic and supportive. Experts indicate that early diagnosis of ocular abnormalities may be important in helping to ensure optimal visual development. In some cases, corrective glasses, other visual aids, and/or surgery may be recommended to help improve vision. In addition, for those with increasing fluid pressure in the eyes or glaucoma, treatment may include measures to help control pressure within the eyes (intraocular pressure), such as therapy with medicated eye drops; laser therapy to create a hole in the colored region of the eye (laser iridectomy) or surgical removal of part of the iris (iridotomy); removal of the lens; and/or other techniques.Experts indicate that stimulating contraction (miosis) or dilation (mydriasis) of the pupils may induce glaucoma in some affected individuals. Therefore, therapy with medications that cause the pupils to contract must be avoided (i.e., are contraindicated) and dilation of the eyes should be done with extreme care.Affected individuals should notify their physician of this diagnosis prior to receiving anesthesia. Joint stiffness and craniofacial abnormalities can influence airway management.Genetic counseling is recommended for individuals with Weill-Marchesani syndrome and their families. Other treatment for this disorder is symptomatic and supportive.
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Weill Marchesani Syndrome
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nord_1288_0
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Overview of Weismann Netter Stuhl Syndrome
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Weismann-Netter-Stuhl syndrome is an extremely rare genetic skeletal disorder characterized by the abnormal development of bone (osseousbo dysplasia). Affected individuals exhibit bowing of the long portions (shafts) of the shinbone (tibia) and the outer, smaller bone of the leg below the knee (fibula). In some individuals, other bones may also be affected, such as the ribs, pelvis, spinal column, and/or bones in the arms. Affected individuals will have some degree of short stature, which means that they are shorter than would otherwise be expected based on their gender and age. The medical definition states that short stature is two standard deviations or more below the mean for children of the same age and gender. The final height of affected individuals will vary. Researchers believe that alterations (mutations) in a gene result in Weismann-Netter-Stuhl syndrome. However, they have not been able to find such a gene. Researchers also believe that the disorder is inherited in an autosomal dominant manner.
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Overview of Weismann Netter Stuhl Syndrome. Weismann-Netter-Stuhl syndrome is an extremely rare genetic skeletal disorder characterized by the abnormal development of bone (osseousbo dysplasia). Affected individuals exhibit bowing of the long portions (shafts) of the shinbone (tibia) and the outer, smaller bone of the leg below the knee (fibula). In some individuals, other bones may also be affected, such as the ribs, pelvis, spinal column, and/or bones in the arms. Affected individuals will have some degree of short stature, which means that they are shorter than would otherwise be expected based on their gender and age. The medical definition states that short stature is two standard deviations or more below the mean for children of the same age and gender. The final height of affected individuals will vary. Researchers believe that alterations (mutations) in a gene result in Weismann-Netter-Stuhl syndrome. However, they have not been able to find such a gene. Researchers also believe that the disorder is inherited in an autosomal dominant manner.
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Weismann Netter Stuhl Syndrome
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nord_1288_1
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Symptoms of Weismann Netter Stuhl Syndrome
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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 people identified with this disorder, the lack of large clinical studies, and the underlying cause of the disorder being unknown 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 the symptoms discussed below. Parents should talk to their children’s physicians and medical team about their specific case, associated symptoms and overall prognosis.
The major physical characteristics of Weismann-Netter-Stuhl syndrome include short stature and bowing of the front (anterior) of the long portions (shafts) of the shinbone (tibia) and the smaller bone of the leg below the knee (fibula). Sometimes the long bone of the thigh (femur) is bowed. Many affected individuals do not have any major functional limitations, and a diagnosis of Weismann-Netter-Stuhl syndrome may not be made until adolescence or adulthood because of the lack of serious complications associated with this disorder. Usually both legs are affected (bilateral). In extremely rare instances, only one leg is affected (unilateral). Along with the characteristic bowing of the tibia and fibula, affected individuals may also exhibit bowing of the sides (lateral bowing) of the thigh bones (femur) and/or outward curvature of the tibia (saber shins). Benign (non-cancerous) overgrowths of cartilage called exostoses may affect the tibias. Additional bones may also be affected including the ribs and pelvis. Affected individuals may also exhibit bowing of certain bones in the forearms (i.e., ulna and radius), malformation of a part of the hip bone (ilium), improper development of bone toward the bottom of the spinal column (horizontal sacrum), widening of the marrow cavities inside bones, and/or thickening of the outer layers (cortexes) of the long bones (diaphyseal dysplasia). Sometimes, a hip deformity in which the thigh bone is angled toward the center of body (coxa vara) is present. In addition, some affected individuals may exhibit a sideways curvature of the spine (scoliosis), an inward curvature of the back (lordosis) so that the back curves into the body, and/or a front-to-back curvature of the spine (kyphosis) so that the upper back is rounded. Most affected individuals begin to walk later than is normally expected, however, the reason for this delay is not understood.There have been reports of intellectual disability in some children as well as an enlarged thyroid (goiter) and low levels of circulating red blood cells (anemia). However, some researchers believe that these findings may be coincidental and not features of Weismann-Netter-Stuhl syndrome.
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Symptoms of Weismann Netter Stuhl 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 people identified with this disorder, the lack of large clinical studies, and the underlying cause of the disorder being unknown 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 the symptoms discussed below. Parents should talk to their children’s physicians and medical team about their specific case, associated symptoms and overall prognosis.
The major physical characteristics of Weismann-Netter-Stuhl syndrome include short stature and bowing of the front (anterior) of the long portions (shafts) of the shinbone (tibia) and the smaller bone of the leg below the knee (fibula). Sometimes the long bone of the thigh (femur) is bowed. Many affected individuals do not have any major functional limitations, and a diagnosis of Weismann-Netter-Stuhl syndrome may not be made until adolescence or adulthood because of the lack of serious complications associated with this disorder. Usually both legs are affected (bilateral). In extremely rare instances, only one leg is affected (unilateral). Along with the characteristic bowing of the tibia and fibula, affected individuals may also exhibit bowing of the sides (lateral bowing) of the thigh bones (femur) and/or outward curvature of the tibia (saber shins). Benign (non-cancerous) overgrowths of cartilage called exostoses may affect the tibias. Additional bones may also be affected including the ribs and pelvis. Affected individuals may also exhibit bowing of certain bones in the forearms (i.e., ulna and radius), malformation of a part of the hip bone (ilium), improper development of bone toward the bottom of the spinal column (horizontal sacrum), widening of the marrow cavities inside bones, and/or thickening of the outer layers (cortexes) of the long bones (diaphyseal dysplasia). Sometimes, a hip deformity in which the thigh bone is angled toward the center of body (coxa vara) is present. In addition, some affected individuals may exhibit a sideways curvature of the spine (scoliosis), an inward curvature of the back (lordosis) so that the back curves into the body, and/or a front-to-back curvature of the spine (kyphosis) so that the upper back is rounded. Most affected individuals begin to walk later than is normally expected, however, the reason for this delay is not understood.There have been reports of intellectual disability in some children as well as an enlarged thyroid (goiter) and low levels of circulating red blood cells (anemia). However, some researchers believe that these findings may be coincidental and not features of Weismann-Netter-Stuhl syndrome.
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Weismann Netter Stuhl Syndrome
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nord_1288_2
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Causes of Weismann Netter Stuhl Syndrome
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The exact, underlying cause of Weismann-Netter-Stuhl syndrome is unknown. Sometimes, the disorder runs in families. Researchers believe it is most likely caused by a change in a gene. However, no genes have been identified to be associated with the disorder. 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 protein, this can affect many organ systems of the body.Although no altered genes have been identified to be associated with Weismann-Netter-Stuhl syndrome, researchers believe that the disorder is inherited in an autosomal dominant manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular 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 an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Causes of Weismann Netter Stuhl Syndrome. The exact, underlying cause of Weismann-Netter-Stuhl syndrome is unknown. Sometimes, the disorder runs in families. Researchers believe it is most likely caused by a change in a gene. However, no genes have been identified to be associated with the disorder. 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 protein, this can affect many organ systems of the body.Although no altered genes have been identified to be associated with Weismann-Netter-Stuhl syndrome, researchers believe that the disorder is inherited in an autosomal dominant manner. Most genetic diseases are determined by the status of the two copies of a gene, one received from the father and one from the mother. Dominant genetic disorders occur when only a single copy of an abnormal gene is necessary to cause a particular 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 an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.
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Affects of Weismann Netter Stuhl Syndrome
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Weismann-Netter-Stuhl syndrome is an extremely rare skeletal disorder that affects males and females in equal numbers. Approximately 70 people have been reported in the medical literature since the disorder’s original description in 1954. However, because rare disorders like Weismann-Netter-Stuhl syndrome often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency in the general population.
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Affects of Weismann Netter Stuhl Syndrome. Weismann-Netter-Stuhl syndrome is an extremely rare skeletal disorder that affects males and females in equal numbers. Approximately 70 people have been reported in the medical literature since the disorder’s original description in 1954. However, because rare disorders like Weismann-Netter-Stuhl syndrome often go unrecognized, these disorders are under-diagnosed, making it difficult to determine the true frequency in the general population.
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Related disorders of Weismann Netter Stuhl Syndrome
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Symptoms of the following disorders can be similar to those of Weismann-Netter-Stuhl syndrome. Comparisons may be useful for a differential diagnosis:Campomelic syndrome is a rare congenital skeletal disorder characterized by short stature along with bowing and an unusual angular shape of the long bones of the legs. Congenital means that the symptoms are present at birth. The bones of the shoulders and pelvic area are often abnormal. Affected individuals may have 11 pairs of ribs instead of the usual 12. There are two forms of this disorder, the long-limbed form and the short-limbed form. The disorder may cause life-threatening complications in infancy because of breathing (respiratory) problems that result from a small chest size and underdevelopment (hypoplasia) of the windpipe and the airways that carry air into the lungs (bronchi). Campomelic syndrome is caused by changes to the SOX9 gene and is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Campomelic” as your search term in the Rare Disease Database.) Vitamin-D deficiency rickets, a disorder that often becomes apparent during infancy or childhood, results from insufficient vitamin D caused by poor nutrition, a lack of exposure to the sun, or malabsorption syndromes in which the intestines do not adequately absorb nutrients including vitamin D added to foods. Vitamin D is needed for calcium and phosphorus absorption from food into the body, which, in turn affects how calcium is deposited in the bones. Thus, adequate vitamin D is essential for proper bone development and growth. Major symptoms of vitamin D deficiency rickets include bone softening and slow growth. Bowing of the legs is very common in this disorder. Vitamin-D deficiency rickets is much more common than Weismann-Netter-Stuhl syndrome, and is quite common in certain areas of the world. (For more information on this disorder, choose “vitamin-D deficiency rickets” as your search term in the Rare Disease Database.)X-linked hypophosphatemia (XLH) is a rare inherited disorder characterized by impaired transport of phosphate and altered vitamin-D activation in the kidneys. In addition, phosphate may not be well-absorbed from the intestines. The low blood phosphate level (hypophosphatemia) resulting from these impairments can lead to rickets or softening of bones (osteomalacia). In childhood bone disease, bowing deformities of the legs from progressive softening of the bone occurs. In adults, the growth plate is no longer open so that osteomalacia is the bone problem. In children, growth rates may be slower than normal, frequently resulting in short stature. X-linked hypophosphatemia is caused by mutations in the PHEX gene located on the X chromosome. It is the most common heritable form of hypophosphatemia. However, autosomal dominant and recessive forms of hypophosphatemia occur as well. (For more information on this disorder, choose “familial hypophosphatemia” as your search term in the Rare Disease Database.)Hypophosphatasia (HPP) is a rare genetic disorder characterized by the abnormal development of bones and teeth. These abnormalities occur due to defective mineralization, the process by which bones and teeth take up minerals such as calcium and phosphorus. These minerals are required for proper hardness and strength. Defective mineralization results in bones that are soft and prone to fracture and deformity. Defective mineralization of teeth can lead to premature tooth loss. The specific symptoms can vary greatly from one person to another, sometimes even among members of the same family. There are five major clinical forms of HPP that range from an extremely severe form that can cause stillbirth to a form associated with only premature loss of baby (deciduous) teeth, but no bone abnormalities. The prenatal benign form of hypophosphatasia is associated with bowed arms and legs at birth. Hypophosphatasia is caused by mutations in the tissue nonspecific alkaline phosphatase (ALPL) gene. This gene is also known as the TNSALP gene. Such mutations lead to low levels of the tissue nonspecific alkaline phosphatase enzyme. Depending on the specific form, hypophosphatasia can be inherited in an autosomal recessive or autosomal dominant manner. (For more information on this disorder, choose “hypophosphatasia” as your search term in the Rare Disease Database.)Ollier disease is a rare skeletal disorder characterized by abnormal bone development (skeletal dysplasia). This disorder is present at birth (congenital), however, it may not be apparent until early childhood when certain symptoms, such as deformities or improper limb growth, are observed. Ollier disease manifests as greater than normal growth of the cartilage in the long bones of the legs and arms so that growth is abnormal and the outer layer (cortical bone) of the bone becomes thin and more fragile. These masses of cartilage are benign (non-cancerous) tumors known as enchondromas. Ollier disease primarily affects the long bones and cartilage in the joints of the arms and legs. Limb shortening, bowing of the long bones, and/or short stature may occur in some affected individuals. The exact cause of Ollier disease is not known. (For more information on this disorder, choose “Ollier” as your search term in the Rare Disease Database.)Congenital syphilis is a rare chronic infectious disorder characterized by low birth weight, fever, rash, and/or outward curvature of the tibia (saber shins). Other symptoms may include hardening of the umbilical cord, high levels of cholesterol at birth, anemia, an enlarged liver and/or spleen, and/or intellectual disability. Syphilis is caused by a spiral-shaped bacteria (spirochete) Treponema pallidum; in newborns with congenital syphilis the disease is acquired by the fetus from the mother sometime during fetal development. In most instances, symptoms of this disorder are apparent at birth or within the first few months of life; however, in some instances, several years may pass before symptoms are recognized. (For more information on this disorder, choose “Congenital Syphilis” as your search term in the Rare Disease Database.)There are many other disorders that can cause similar symptoms to Weismann-Netter-Stuhl syndrome including certain forms of Ehlers-Danlos syndrome, Paget disease, osteogenesis imperfecta, renal osteodystrophy, tibia vara (Blount disease), fibrous dysplasia, achondroplasia, neurofibromatosis, congenital bowing of certain bones, and developmental bowing of certain bones. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of Weismann Netter Stuhl Syndrome. Symptoms of the following disorders can be similar to those of Weismann-Netter-Stuhl syndrome. Comparisons may be useful for a differential diagnosis:Campomelic syndrome is a rare congenital skeletal disorder characterized by short stature along with bowing and an unusual angular shape of the long bones of the legs. Congenital means that the symptoms are present at birth. The bones of the shoulders and pelvic area are often abnormal. Affected individuals may have 11 pairs of ribs instead of the usual 12. There are two forms of this disorder, the long-limbed form and the short-limbed form. The disorder may cause life-threatening complications in infancy because of breathing (respiratory) problems that result from a small chest size and underdevelopment (hypoplasia) of the windpipe and the airways that carry air into the lungs (bronchi). Campomelic syndrome is caused by changes to the SOX9 gene and is inherited as an autosomal recessive trait. (For more information on this disorder, choose “Campomelic” as your search term in the Rare Disease Database.) Vitamin-D deficiency rickets, a disorder that often becomes apparent during infancy or childhood, results from insufficient vitamin D caused by poor nutrition, a lack of exposure to the sun, or malabsorption syndromes in which the intestines do not adequately absorb nutrients including vitamin D added to foods. Vitamin D is needed for calcium and phosphorus absorption from food into the body, which, in turn affects how calcium is deposited in the bones. Thus, adequate vitamin D is essential for proper bone development and growth. Major symptoms of vitamin D deficiency rickets include bone softening and slow growth. Bowing of the legs is very common in this disorder. Vitamin-D deficiency rickets is much more common than Weismann-Netter-Stuhl syndrome, and is quite common in certain areas of the world. (For more information on this disorder, choose “vitamin-D deficiency rickets” as your search term in the Rare Disease Database.)X-linked hypophosphatemia (XLH) is a rare inherited disorder characterized by impaired transport of phosphate and altered vitamin-D activation in the kidneys. In addition, phosphate may not be well-absorbed from the intestines. The low blood phosphate level (hypophosphatemia) resulting from these impairments can lead to rickets or softening of bones (osteomalacia). In childhood bone disease, bowing deformities of the legs from progressive softening of the bone occurs. In adults, the growth plate is no longer open so that osteomalacia is the bone problem. In children, growth rates may be slower than normal, frequently resulting in short stature. X-linked hypophosphatemia is caused by mutations in the PHEX gene located on the X chromosome. It is the most common heritable form of hypophosphatemia. However, autosomal dominant and recessive forms of hypophosphatemia occur as well. (For more information on this disorder, choose “familial hypophosphatemia” as your search term in the Rare Disease Database.)Hypophosphatasia (HPP) is a rare genetic disorder characterized by the abnormal development of bones and teeth. These abnormalities occur due to defective mineralization, the process by which bones and teeth take up minerals such as calcium and phosphorus. These minerals are required for proper hardness and strength. Defective mineralization results in bones that are soft and prone to fracture and deformity. Defective mineralization of teeth can lead to premature tooth loss. The specific symptoms can vary greatly from one person to another, sometimes even among members of the same family. There are five major clinical forms of HPP that range from an extremely severe form that can cause stillbirth to a form associated with only premature loss of baby (deciduous) teeth, but no bone abnormalities. The prenatal benign form of hypophosphatasia is associated with bowed arms and legs at birth. Hypophosphatasia is caused by mutations in the tissue nonspecific alkaline phosphatase (ALPL) gene. This gene is also known as the TNSALP gene. Such mutations lead to low levels of the tissue nonspecific alkaline phosphatase enzyme. Depending on the specific form, hypophosphatasia can be inherited in an autosomal recessive or autosomal dominant manner. (For more information on this disorder, choose “hypophosphatasia” as your search term in the Rare Disease Database.)Ollier disease is a rare skeletal disorder characterized by abnormal bone development (skeletal dysplasia). This disorder is present at birth (congenital), however, it may not be apparent until early childhood when certain symptoms, such as deformities or improper limb growth, are observed. Ollier disease manifests as greater than normal growth of the cartilage in the long bones of the legs and arms so that growth is abnormal and the outer layer (cortical bone) of the bone becomes thin and more fragile. These masses of cartilage are benign (non-cancerous) tumors known as enchondromas. Ollier disease primarily affects the long bones and cartilage in the joints of the arms and legs. Limb shortening, bowing of the long bones, and/or short stature may occur in some affected individuals. The exact cause of Ollier disease is not known. (For more information on this disorder, choose “Ollier” as your search term in the Rare Disease Database.)Congenital syphilis is a rare chronic infectious disorder characterized by low birth weight, fever, rash, and/or outward curvature of the tibia (saber shins). Other symptoms may include hardening of the umbilical cord, high levels of cholesterol at birth, anemia, an enlarged liver and/or spleen, and/or intellectual disability. Syphilis is caused by a spiral-shaped bacteria (spirochete) Treponema pallidum; in newborns with congenital syphilis the disease is acquired by the fetus from the mother sometime during fetal development. In most instances, symptoms of this disorder are apparent at birth or within the first few months of life; however, in some instances, several years may pass before symptoms are recognized. (For more information on this disorder, choose “Congenital Syphilis” as your search term in the Rare Disease Database.)There are many other disorders that can cause similar symptoms to Weismann-Netter-Stuhl syndrome including certain forms of Ehlers-Danlos syndrome, Paget disease, osteogenesis imperfecta, renal osteodystrophy, tibia vara (Blount disease), fibrous dysplasia, achondroplasia, neurofibromatosis, congenital bowing of certain bones, and developmental bowing of certain bones. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Diagnosis of Weismann Netter Stuhl Syndrome
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The diagnosis of Weismann-Netter-Stuhl syndrome may be confirmed by x-ray studies of the skeleton that reveal distinctive bowing of the long bones of the legs, lateral bowing of the femur, thickened outer layers of bones, and widened marrow cavities. Other x-ray findings may include bowing of certain arm bones (i.e., ulna and radius), malformation of part of the hip bone (ilium), abnormal development of part of the spinal column (horizontal sacrum), and/or hardening of a membrane that surrounds the brain and spinal cord (dural calcification).A diagnosis of Weismann-Netter-Stuhl syndrome is difficult and often delayed because the disorder is not well known, the exact cause has not been identified, and it can be mistaken for many other disorders.
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Diagnosis of Weismann Netter Stuhl Syndrome. The diagnosis of Weismann-Netter-Stuhl syndrome may be confirmed by x-ray studies of the skeleton that reveal distinctive bowing of the long bones of the legs, lateral bowing of the femur, thickened outer layers of bones, and widened marrow cavities. Other x-ray findings may include bowing of certain arm bones (i.e., ulna and radius), malformation of part of the hip bone (ilium), abnormal development of part of the spinal column (horizontal sacrum), and/or hardening of a membrane that surrounds the brain and spinal cord (dural calcification).A diagnosis of Weismann-Netter-Stuhl syndrome is difficult and often delayed because the disorder is not well known, the exact cause has not been identified, and it can be mistaken for many other disorders.
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Therapies of Weismann Netter Stuhl Syndrome
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Treatment
The treatment of Weismann-Netter-Stuhl syndrome is directed toward the specific symptoms that are apparent in each individual. Genetic counseling will be of benefit for affected individuals and their families. A supportive team approach for children with Weismann-Netter-Stuhl syndrome may be helpful. Such a team approach may include physical therapy and other medical, social, or vocational services. For many people, the skeletal abnormalities do not disturb the functions of the legs or only mildly affect function. One journal article recommended surgical intervention for Weismann-Netter-Stuhl syndrome (Gupta 2014). However, if the abnormalities of the legs are not causing any functional problems, then surgery is not necessary. Decisions concerning treatment can vary for each affected individual depending on several factors including their age, severity of the skeletal malformation and misalignment, an individual’s overall health, patient preference and other appropriate factors.
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Therapies of Weismann Netter Stuhl Syndrome. Treatment
The treatment of Weismann-Netter-Stuhl syndrome is directed toward the specific symptoms that are apparent in each individual. Genetic counseling will be of benefit for affected individuals and their families. A supportive team approach for children with Weismann-Netter-Stuhl syndrome may be helpful. Such a team approach may include physical therapy and other medical, social, or vocational services. For many people, the skeletal abnormalities do not disturb the functions of the legs or only mildly affect function. One journal article recommended surgical intervention for Weismann-Netter-Stuhl syndrome (Gupta 2014). However, if the abnormalities of the legs are not causing any functional problems, then surgery is not necessary. Decisions concerning treatment can vary for each affected individual depending on several factors including their age, severity of the skeletal malformation and misalignment, an individual’s overall health, patient preference and other appropriate factors.
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Overview of Werner Syndrome
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Werner syndrome is a rare progressive disorder that is characterized by the appearance of unusually accelerated aging (progeria). Although the disorder is typically recognized by the third or fourth decades of life, certain characteristic findings are present beginning during adolescence and early adulthood.Individuals with Werner syndrome have an abnormally slow growth rate and growth stops at puberty. As a result, affected individuals have short stature and low weight relative to height. By age 25, those with the disorder typically experience early graying and premature loss of scalp hair (alopecia). As the disease progresses, additional abnormalities include loss of the layer of fat beneath the skin (subcutaneous adipose tissue); severe wasting (atrophy) of muscle tissue in certain areas of the body; and degenerative skin changes, particularly in the facial area, the upper arms and hands and the lower legs and feet (distal extremities). Due to degenerative changes affecting the facial area, individuals with Werner syndrome may have unusually prominent eyes, a beaked or pinched nose and/or other characteristic facial abnormalities.Werner syndrome may also be characterized by development of a distinctive high-pitched voice; eye abnormalities, including premature clouding of the lenses of the eyes (bilateral senile cataracts); and certain endocrine defects, such as impaired functioning of the ovaries in females or testes in males (hypogonadism) or abnormal production of the hormone insulin by the pancreas and resistance to the effects of insulin (non-insulin-dependent diabetes mellitus). In addition, individuals with Werner syndrome may develop progressive thickening and loss of elasticity of artery walls (arteriosclerosis). Affected blood vessels typically include the arteries that transport oxygen-rich (oxygenated) blood to heart muscle (coronary arteries). Some affected individuals may also be susceptible to developing certain benign (noncancerous) or malignant tumors. Progressive arteriosclerosis, malignancies, and/or associated abnormalities may result in potentially life-threatening complications by approximately the fourth or fifth decade of life. Werner syndrome is inherited in an autosomal recessive pattern.
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Overview of Werner Syndrome. Werner syndrome is a rare progressive disorder that is characterized by the appearance of unusually accelerated aging (progeria). Although the disorder is typically recognized by the third or fourth decades of life, certain characteristic findings are present beginning during adolescence and early adulthood.Individuals with Werner syndrome have an abnormally slow growth rate and growth stops at puberty. As a result, affected individuals have short stature and low weight relative to height. By age 25, those with the disorder typically experience early graying and premature loss of scalp hair (alopecia). As the disease progresses, additional abnormalities include loss of the layer of fat beneath the skin (subcutaneous adipose tissue); severe wasting (atrophy) of muscle tissue in certain areas of the body; and degenerative skin changes, particularly in the facial area, the upper arms and hands and the lower legs and feet (distal extremities). Due to degenerative changes affecting the facial area, individuals with Werner syndrome may have unusually prominent eyes, a beaked or pinched nose and/or other characteristic facial abnormalities.Werner syndrome may also be characterized by development of a distinctive high-pitched voice; eye abnormalities, including premature clouding of the lenses of the eyes (bilateral senile cataracts); and certain endocrine defects, such as impaired functioning of the ovaries in females or testes in males (hypogonadism) or abnormal production of the hormone insulin by the pancreas and resistance to the effects of insulin (non-insulin-dependent diabetes mellitus). In addition, individuals with Werner syndrome may develop progressive thickening and loss of elasticity of artery walls (arteriosclerosis). Affected blood vessels typically include the arteries that transport oxygen-rich (oxygenated) blood to heart muscle (coronary arteries). Some affected individuals may also be susceptible to developing certain benign (noncancerous) or malignant tumors. Progressive arteriosclerosis, malignancies, and/or associated abnormalities may result in potentially life-threatening complications by approximately the fourth or fifth decade of life. Werner syndrome is inherited in an autosomal recessive pattern.
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Symptoms of Werner Syndrome
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Children with Werner syndrome often appear unusually thin and during late childhood, have an unusually slow growth rate. In addition, there is absence of the growth spurt typically seen during adolescence. Affected individuals typically reach their final height by approximately 13 years of age. However, adult height may be reached as early as age 10 or as late as at age 18. Weight is also unusually low, even relative to short stature.Before age 20, most individuals with Werner syndrome develop early graying and whitening of the scalp hair. By about 25 years of age, affected individuals may experience premature loss of scalp hair (alopecia) as well as loss of the eyebrows and eyelashes. In addition, hair under the arms (axillary hair), in the pubic area, and on the trunk may be unusually sparse or absent. According to reports in the medical literature, the hair loss seen in people with Werner syndrome may occur secondary to impaired functioning of the ovaries in females or the testes in males (hypogonadism), an endocrine condition associated with deficient growth and sexual development. Both males and females with Werner syndrome may be affected by hypogonadism. As a result, affected males usually have an unusually small penis and small testes. Some females with the disorder may fail to develop secondary sexual characteristics (e.g., appearance of axillary and pubic hair, breast development, menstruation) and have poorly developed genitals. In other affected females, menstruation may be sparse and irregular. Due to hypogonadism, most people with the disorder are infertile. However, there have been reports in the literature confirming that some affected males and females have reproduced.In addition to premature graying and hair loss, individuals with Werner syndrome are affected by other progressive degenerative changes, including gradual loss of the layer of fat beneath the skin (subcutaneous adipose tissue); severe wasting (atrophy) of muscles within the hands, legs, and feet; and premature, generalized loss of bone density (osteoporosis), a condition that may cause or contribute to repeated fractures following minor trauma. Dental abnormalities may also be present, including abnormal development and premature loss of teeth. In approximately one third of individuals with Werner syndrome, there is also an abnormal accumulation of calcium salts (calcification) in and associated hardening of soft tissues (e.g., ligaments, tendons), particularly those of the elbows, knees, and ankles. In addition, due to progressive atrophy of the vocal cords, most individuals with the disorder develop an abnormally high-pitched voice. In other cases, the voice may be squeaky or unusually hoarse.By approximately 25 years of age, individuals with Werner syndrome also develop progressive skin changes, particularly affecting the facial area, the upper arms and hands, and the lower legs and feet (distal extremities). For example, there is skin wasting (atrophy) over areas in which there is depletion of fatty (adipose), connective, and muscle tissue, resulting in the appearance of unusually shiny, “waxy,” smooth, or hardened (“scleroderma-like”) skin patches that may adhere to underlying tissues. Affected areas may be prone to developing open sores (ulcers) due to decreased supply of oxygenated blood to tissues (ischemia). The ulcers may be chronic and slow healing. Deep ulcerations around Achilles tendons and, less frequently, at elbows, are highly characteristic to Werner syndrome.Many individuals with Werner syndrome also have additional skin abnormalities. Skin of the arms and legs may develop abnormally increased coloration (hyperpigmentation), decreased coloration (hypopigmentation), or abnormal widening of certain small underlying blood vessels, causing associated redness (telangiectasias). In addition, skin of the palms, of the soles, and overlying certain prominent joints, such as the elbows and knees, may become unusually thickened (hyperkeratosis) and tend to develop ulcers due to destruction of surface tissues.Due to atrophic changes of the skin and underlying tissues in the facial area, affected individuals may have a distinctive, “pinched” facial appearance including unusually prominent eyes; stiff ears that have lost their elasticity; and a thin, beaked or pinched nose. Premature graying and loss of hair contribute to the characteristic appearance. According to reports in the medical literature, in most individuals with Werner syndrome, the appearance of premature aging is apparent by approximately age 30 to 40.Werner syndrome is also typically characterized by the premature onset of senile cataracts, a condition in which there is loss of transparency of the lenses of the eyes. In individuals with Werner syndrome, cataracts typically affect both eyes (bilateral) and have an abrupt onset within the third or fourth decade of life. (Senile cataracts typically develop in individuals over age 50.) In some cases, other abnormalities of the eyes may also be present, such as an accumulation of calcium deposits within the transparent region in the front of the eyes (corneal calcification), inflammation of the middle and innermost layers of the eyes (chorioretinitis), degeneration of the nerve cells (rods and cones) of the retina that respond to light (retinitis pigmentosa), and/or progressive degeneration of the central region of the retina (senile macular degeneration). The degree of associated visual impairment depends upon the severity and/or combination of eye abnormalities present.Approximately 70 percent of affected individuals have developed non-insulin-dependent (or type II) diabetes mellitus at the time of diagnosis. Non-insulin-dependent diabetes mellitus is a metabolic disorder characterized by resistance to the effects of the hormone insulin and abnormal insulin secretion by the pancreas, resulting in increased levels of the simple sugar glucose in the blood. (Insulin regulates glucose levels in the blood by promoting the movement of glucose into cells for energy production.) This form of diabetes usually develops in normal individuals of approximately 50 to 60 years. However, in those with Werner syndrome, the condition may become apparent by about age 35. Affected individuals may have no apparent symptoms (asymptomatic) at diagnosis or experience increased urination (polyuria), excessive thirst (polydipsia), increased hunger (polyphagia), and/or other characteristic symptoms. In addition, those with this form of diabetes may be susceptible to diabetic coma due to severely reduced levels of fluid within cells (hyperosmolar nonketotic coma). According to reports in the medical literature, although non-insulin-dependent diabetes mellitus may be associated with certain long-term complications, such as nerve damage (neuropathy), impaired kidney function (nephropathy), and damage to blood vessels within the retina (diabetic retinopathy), such complications have not been reported in affected individuals with Werner syndrome.Werner syndrome is also characterized by severe, progressive, often widespread thickening and loss of elasticity of artery walls (arteriosclerosis). In some affected arteries, there may be abnormal accumulations of calcium deposits within the middle coat (tunica media) of the arteries and progressive destruction and replacement of the arteries’ muscle and elastic fibers with fibrous tissue (Monckeberg’s arteriosclerosis). Arteries affected by this form of arteriosclerosis may include those that transport oxygen-rich blood to heart muscle (coronary arteries) or certain arteries of the legs (peripheral vascular disease). Arteriosclerosis of peripheral blood vessels may cause or aggravate skin wasting (atrophy) and ulceration. In addition, abnormal calcium deposits may accumulate within certain heart valves, such as the valve situated where the body’s major artery (aorta) arises from the lower left chamber of the heart (aortic valve) and the valve located between the left upper and lower heart chambers (mitral valve). Progressive arteriosclerosis may lead to episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks); progressive inability of the heart to effectively pump blood to the lungs and the rest of the body (heart failure); localized loss of heart muscle caused by interruption of its blood supply (myocardial infarction or heart attack); and/or other potentially life-threatening complications.People with Werner syndrome also have an increased predisposition to cancers. The most common neoplasms in Werner syndrome are carcinomas of thyroid, followed by cancers of the pigment-producing cells in skin and mucosa (malignant melanoma), cancer of the protective membranes surrounding the brain and the spinal cord (meningioma), tumors that arise within the soft tissues and bones (sarcomas and osteosarcoma), soft tissue sarcomas, primary bone tumors and leukemia/myelodysplasia.Due to progressive arteriosclerosis, malignancies and/or other associated abnormalities, many individuals with Werner syndrome may experience life-threatening complications by approximately the fourth or fifth decade of life.
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Symptoms of Werner Syndrome. Children with Werner syndrome often appear unusually thin and during late childhood, have an unusually slow growth rate. In addition, there is absence of the growth spurt typically seen during adolescence. Affected individuals typically reach their final height by approximately 13 years of age. However, adult height may be reached as early as age 10 or as late as at age 18. Weight is also unusually low, even relative to short stature.Before age 20, most individuals with Werner syndrome develop early graying and whitening of the scalp hair. By about 25 years of age, affected individuals may experience premature loss of scalp hair (alopecia) as well as loss of the eyebrows and eyelashes. In addition, hair under the arms (axillary hair), in the pubic area, and on the trunk may be unusually sparse or absent. According to reports in the medical literature, the hair loss seen in people with Werner syndrome may occur secondary to impaired functioning of the ovaries in females or the testes in males (hypogonadism), an endocrine condition associated with deficient growth and sexual development. Both males and females with Werner syndrome may be affected by hypogonadism. As a result, affected males usually have an unusually small penis and small testes. Some females with the disorder may fail to develop secondary sexual characteristics (e.g., appearance of axillary and pubic hair, breast development, menstruation) and have poorly developed genitals. In other affected females, menstruation may be sparse and irregular. Due to hypogonadism, most people with the disorder are infertile. However, there have been reports in the literature confirming that some affected males and females have reproduced.In addition to premature graying and hair loss, individuals with Werner syndrome are affected by other progressive degenerative changes, including gradual loss of the layer of fat beneath the skin (subcutaneous adipose tissue); severe wasting (atrophy) of muscles within the hands, legs, and feet; and premature, generalized loss of bone density (osteoporosis), a condition that may cause or contribute to repeated fractures following minor trauma. Dental abnormalities may also be present, including abnormal development and premature loss of teeth. In approximately one third of individuals with Werner syndrome, there is also an abnormal accumulation of calcium salts (calcification) in and associated hardening of soft tissues (e.g., ligaments, tendons), particularly those of the elbows, knees, and ankles. In addition, due to progressive atrophy of the vocal cords, most individuals with the disorder develop an abnormally high-pitched voice. In other cases, the voice may be squeaky or unusually hoarse.By approximately 25 years of age, individuals with Werner syndrome also develop progressive skin changes, particularly affecting the facial area, the upper arms and hands, and the lower legs and feet (distal extremities). For example, there is skin wasting (atrophy) over areas in which there is depletion of fatty (adipose), connective, and muscle tissue, resulting in the appearance of unusually shiny, “waxy,” smooth, or hardened (“scleroderma-like”) skin patches that may adhere to underlying tissues. Affected areas may be prone to developing open sores (ulcers) due to decreased supply of oxygenated blood to tissues (ischemia). The ulcers may be chronic and slow healing. Deep ulcerations around Achilles tendons and, less frequently, at elbows, are highly characteristic to Werner syndrome.Many individuals with Werner syndrome also have additional skin abnormalities. Skin of the arms and legs may develop abnormally increased coloration (hyperpigmentation), decreased coloration (hypopigmentation), or abnormal widening of certain small underlying blood vessels, causing associated redness (telangiectasias). In addition, skin of the palms, of the soles, and overlying certain prominent joints, such as the elbows and knees, may become unusually thickened (hyperkeratosis) and tend to develop ulcers due to destruction of surface tissues.Due to atrophic changes of the skin and underlying tissues in the facial area, affected individuals may have a distinctive, “pinched” facial appearance including unusually prominent eyes; stiff ears that have lost their elasticity; and a thin, beaked or pinched nose. Premature graying and loss of hair contribute to the characteristic appearance. According to reports in the medical literature, in most individuals with Werner syndrome, the appearance of premature aging is apparent by approximately age 30 to 40.Werner syndrome is also typically characterized by the premature onset of senile cataracts, a condition in which there is loss of transparency of the lenses of the eyes. In individuals with Werner syndrome, cataracts typically affect both eyes (bilateral) and have an abrupt onset within the third or fourth decade of life. (Senile cataracts typically develop in individuals over age 50.) In some cases, other abnormalities of the eyes may also be present, such as an accumulation of calcium deposits within the transparent region in the front of the eyes (corneal calcification), inflammation of the middle and innermost layers of the eyes (chorioretinitis), degeneration of the nerve cells (rods and cones) of the retina that respond to light (retinitis pigmentosa), and/or progressive degeneration of the central region of the retina (senile macular degeneration). The degree of associated visual impairment depends upon the severity and/or combination of eye abnormalities present.Approximately 70 percent of affected individuals have developed non-insulin-dependent (or type II) diabetes mellitus at the time of diagnosis. Non-insulin-dependent diabetes mellitus is a metabolic disorder characterized by resistance to the effects of the hormone insulin and abnormal insulin secretion by the pancreas, resulting in increased levels of the simple sugar glucose in the blood. (Insulin regulates glucose levels in the blood by promoting the movement of glucose into cells for energy production.) This form of diabetes usually develops in normal individuals of approximately 50 to 60 years. However, in those with Werner syndrome, the condition may become apparent by about age 35. Affected individuals may have no apparent symptoms (asymptomatic) at diagnosis or experience increased urination (polyuria), excessive thirst (polydipsia), increased hunger (polyphagia), and/or other characteristic symptoms. In addition, those with this form of diabetes may be susceptible to diabetic coma due to severely reduced levels of fluid within cells (hyperosmolar nonketotic coma). According to reports in the medical literature, although non-insulin-dependent diabetes mellitus may be associated with certain long-term complications, such as nerve damage (neuropathy), impaired kidney function (nephropathy), and damage to blood vessels within the retina (diabetic retinopathy), such complications have not been reported in affected individuals with Werner syndrome.Werner syndrome is also characterized by severe, progressive, often widespread thickening and loss of elasticity of artery walls (arteriosclerosis). In some affected arteries, there may be abnormal accumulations of calcium deposits within the middle coat (tunica media) of the arteries and progressive destruction and replacement of the arteries’ muscle and elastic fibers with fibrous tissue (Monckeberg’s arteriosclerosis). Arteries affected by this form of arteriosclerosis may include those that transport oxygen-rich blood to heart muscle (coronary arteries) or certain arteries of the legs (peripheral vascular disease). Arteriosclerosis of peripheral blood vessels may cause or aggravate skin wasting (atrophy) and ulceration. In addition, abnormal calcium deposits may accumulate within certain heart valves, such as the valve situated where the body’s major artery (aorta) arises from the lower left chamber of the heart (aortic valve) and the valve located between the left upper and lower heart chambers (mitral valve). Progressive arteriosclerosis may lead to episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks); progressive inability of the heart to effectively pump blood to the lungs and the rest of the body (heart failure); localized loss of heart muscle caused by interruption of its blood supply (myocardial infarction or heart attack); and/or other potentially life-threatening complications.People with Werner syndrome also have an increased predisposition to cancers. The most common neoplasms in Werner syndrome are carcinomas of thyroid, followed by cancers of the pigment-producing cells in skin and mucosa (malignant melanoma), cancer of the protective membranes surrounding the brain and the spinal cord (meningioma), tumors that arise within the soft tissues and bones (sarcomas and osteosarcoma), soft tissue sarcomas, primary bone tumors and leukemia/myelodysplasia.Due to progressive arteriosclerosis, malignancies and/or other associated abnormalities, many individuals with Werner syndrome may experience life-threatening complications by approximately the fourth or fifth decade of life.
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Causes of Werner Syndrome
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Werner syndrome is caused by changes (mutations or variants) in the WRN gene. More than 80 different mutations of the WRN gene have been identified in individuals with the disorder.The WRN gene encodes for a “helicase” protein, suggesting that impaired DNA metabolism is involved in the premature aging seen in individuals with the disorder. Metabolism refers to the chemical processes occurring within bodily tissues. DNA or deoxyribonucleic acid, which is the carrier of the genetic code within cells, has a coiled (helical), ladder-like structure and is composed of strands of particular chemical groups. DNA “helicase” proteins are thought to promote the “unwinding” of DNA during certain cellular activities, such as the repair of damaged DNA and the separation of identical chromosomes (chromosomal segregation) into two “daughter cells” during cellular division and reproduction. Researchers suggest that Werner syndrome is due to complete loss of function of the helicase protein encoded by the WRN gene. The specific function of the helicase protein in preventing premature aging remains unclear.However, during laboratory (in vitro) studies of samples of skin cells (cultured human fibroblasts), researchers have demonstrated that the cells from individuals without the disorder may multiply approximately 60 times (“population doublings”) whereas Werner syndrome fibroblasts may reproduce only up to about 20 times. Due to such findings, some researchers have suggested that WRN is essentially a “counting gene,” regulating the total number of times that human cells may divide and reproduce. Researchers speculate that variants in the WRN gene may result in premature inhibition of DNA replication processes (synthesis) and early cellular aging (senescence), events that typically occur later in normal, aging human cells.Researchers have also observed a high frequency of chromosomal abnormalities (e.g., random translocations) in cultured skin cells (fibroblasts) and cultured white blood cells (lymphocytes) derived from certain cell lines (clones) in individuals with Werner syndrome. Such findings (sometimes referred to as “variegated translocation mosaicism”) suggest that “chromosome breakage” may be characteristic of or play some role in the disease process. However, the specific implications of such findings remain unknown and further research is required.Werner syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females.The parents of some individuals with Werner syndrome have been closely related by blood (consanguineous). If both parents carry the same disease gene, there is a higher-than-normal risk that their children may inherit the two disease genes necessary for the development of the disease.
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Causes of Werner Syndrome. Werner syndrome is caused by changes (mutations or variants) in the WRN gene. More than 80 different mutations of the WRN gene have been identified in individuals with the disorder.The WRN gene encodes for a “helicase” protein, suggesting that impaired DNA metabolism is involved in the premature aging seen in individuals with the disorder. Metabolism refers to the chemical processes occurring within bodily tissues. DNA or deoxyribonucleic acid, which is the carrier of the genetic code within cells, has a coiled (helical), ladder-like structure and is composed of strands of particular chemical groups. DNA “helicase” proteins are thought to promote the “unwinding” of DNA during certain cellular activities, such as the repair of damaged DNA and the separation of identical chromosomes (chromosomal segregation) into two “daughter cells” during cellular division and reproduction. Researchers suggest that Werner syndrome is due to complete loss of function of the helicase protein encoded by the WRN gene. The specific function of the helicase protein in preventing premature aging remains unclear.However, during laboratory (in vitro) studies of samples of skin cells (cultured human fibroblasts), researchers have demonstrated that the cells from individuals without the disorder may multiply approximately 60 times (“population doublings”) whereas Werner syndrome fibroblasts may reproduce only up to about 20 times. Due to such findings, some researchers have suggested that WRN is essentially a “counting gene,” regulating the total number of times that human cells may divide and reproduce. Researchers speculate that variants in the WRN gene may result in premature inhibition of DNA replication processes (synthesis) and early cellular aging (senescence), events that typically occur later in normal, aging human cells.Researchers have also observed a high frequency of chromosomal abnormalities (e.g., random translocations) in cultured skin cells (fibroblasts) and cultured white blood cells (lymphocytes) derived from certain cell lines (clones) in individuals with Werner syndrome. Such findings (sometimes referred to as “variegated translocation mosaicism”) suggest that “chromosome breakage” may be characteristic of or play some role in the disease process. However, the specific implications of such findings remain unknown and further research is required.Werner syndrome is inherited in an autosomal recessive pattern. Recessive genetic disorders occur when an individual inherits an abnormal gene from each parent. If an individual receives one normal gene and one abnormal 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 abnormal 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 is 25%. The risk is the same for males and females.The parents of some individuals with Werner syndrome have been closely related by blood (consanguineous). If both parents carry the same disease gene, there is a higher-than-normal risk that their children may inherit the two disease genes necessary for the development of the disease.
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Affects of Werner Syndrome
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Werner syndrome is a rare disorder that affects males and females in equal numbers. Since the disorder was originally described in the medical literature in 1904 (O. Werner), more than 800 patients have been reported. The disorder’s frequency has been estimated at one to 20 per one million individuals in the United States. Although certain associated findings are present beginning during childhood, puberty and young adulthood, the disorder is most frequently recognized in the third or fourth decades of life.
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Affects of Werner Syndrome. Werner syndrome is a rare disorder that affects males and females in equal numbers. Since the disorder was originally described in the medical literature in 1904 (O. Werner), more than 800 patients have been reported. The disorder’s frequency has been estimated at one to 20 per one million individuals in the United States. Although certain associated findings are present beginning during childhood, puberty and young adulthood, the disorder is most frequently recognized in the third or fourth decades of life.
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Related disorders of Werner Syndrome
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Symptoms of the following disorders can be similar to those of Werner syndrome. Comparisons may be useful for a differential diagnosis:Hutchinson-Gilford progeria syndrome is a very rare disorder of childhood characterized by premature aging, short stature, and characteristic facial features. The primary symptoms of this disorder are those associated with the aging process. Children with this disease age very rapidly and suffer with disorders of the aged while they are young. At approximately 10 years of age, most children with Hutchinson-Gilford progeria syndrome attain the height of an average 3-year-old child. Arthritis often affects bone joints during childhood and adolescence. (For more information on this disorder, choose “Hutchinson-Gilford Progeria” as your search term in the Rare Disease Database.)Gottron’s syndrome (acrogeria) is a mild, inherited form of premature aging (progeria) characterized by abnormally small hands and feet with thin and delicate skin. From infancy on, children with this disorder appear older than their actual age. The skin is unusually thin and parchment-like on the hands and feet. The hands and feet remain abnormally small into adulthood. (For more information on this disorder, choose “Gottron” as your search term in the Rare Disease Database.)De Barsy syndrome is a rare disorder that is inherited in an autosomal recessive pattern. The main characteristics include degeneration of the elastic tissue in the skin (cutis laxa), involuntary movements of the arms and legs (athetosis), cloudy corneas of the eyes, large prominent ears and loss of muscle tone. Other symptoms may include unusual flexibility of the small joints, a forehead that protrudes outward (frontal bossing), and/or short stature. The loss of elasticity of the skin leads to an aged, wrinkled appearance. (For more information on this disorder, choose “De Barsy” as your search term in the Rare Disease Database.)Mulvihill-Smith syndrome is an extremely rare inherited disorder associated with premature aging. It is characterized by short stature, a small head (microcephaly), an aged appearance to the face, the loss of fatty layers under the skin (subcutaneous), multiple pigmented skin blemishes (nevi), hearing loss and/or deficiencies of the immune system. This disease can occur in childhood or adolescence. Mulvihill-Smith syndrome has been reported in only four individuals in the medical literature.Storm syndrome (Werner-like syndrome) is an extremely rare inherited disorder associated with premature aging and heart disease. Other symptoms during adolescence may include the loss of eyebrows and eyelashes, and the thinning and graying of scalp hair. The skin over the hands and face becomes tight with a wrinkled appearance. Some affected individuals also have pain and impairment of joint function.Combined defect of growth factors (Werner-like syndrome due to combined growth factor deficiency) is an extremely rare inherited disorder. The symptoms of this disorder are similar to those of Werner syndrome and include the loss of the fatty layers on the arms and legs, a beak-like nose, a small jaw, and/or a narrow mouth. Other symptoms may include impaired joint function, flat feet, and thin, tight skin.Rothmund-Thomson syndrome is an inherited skin disorder characterized by abnormal redness of the skin caused by congested and obstructed small blood vessels (capillaries). Eventually the capillaries may become obstructed. Most people with Rothmund-Thomson syndrome have small stature, loss of muscle and red coloring of the skin. Some people are abnormally sensitive to light (photosensitivity) and may develop cataracts during adolescence. Other symptoms may include underdeveloped teeth and nails, unusually small hands and feet, malformed or missing thumbs and/or sparse and prematurely gray hair or baldness. (For more information on this disorder, choose “Rothmund-Thomson” as your search term in the Rare Disease Database.)
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Related disorders of Werner Syndrome. Symptoms of the following disorders can be similar to those of Werner syndrome. Comparisons may be useful for a differential diagnosis:Hutchinson-Gilford progeria syndrome is a very rare disorder of childhood characterized by premature aging, short stature, and characteristic facial features. The primary symptoms of this disorder are those associated with the aging process. Children with this disease age very rapidly and suffer with disorders of the aged while they are young. At approximately 10 years of age, most children with Hutchinson-Gilford progeria syndrome attain the height of an average 3-year-old child. Arthritis often affects bone joints during childhood and adolescence. (For more information on this disorder, choose “Hutchinson-Gilford Progeria” as your search term in the Rare Disease Database.)Gottron’s syndrome (acrogeria) is a mild, inherited form of premature aging (progeria) characterized by abnormally small hands and feet with thin and delicate skin. From infancy on, children with this disorder appear older than their actual age. The skin is unusually thin and parchment-like on the hands and feet. The hands and feet remain abnormally small into adulthood. (For more information on this disorder, choose “Gottron” as your search term in the Rare Disease Database.)De Barsy syndrome is a rare disorder that is inherited in an autosomal recessive pattern. The main characteristics include degeneration of the elastic tissue in the skin (cutis laxa), involuntary movements of the arms and legs (athetosis), cloudy corneas of the eyes, large prominent ears and loss of muscle tone. Other symptoms may include unusual flexibility of the small joints, a forehead that protrudes outward (frontal bossing), and/or short stature. The loss of elasticity of the skin leads to an aged, wrinkled appearance. (For more information on this disorder, choose “De Barsy” as your search term in the Rare Disease Database.)Mulvihill-Smith syndrome is an extremely rare inherited disorder associated with premature aging. It is characterized by short stature, a small head (microcephaly), an aged appearance to the face, the loss of fatty layers under the skin (subcutaneous), multiple pigmented skin blemishes (nevi), hearing loss and/or deficiencies of the immune system. This disease can occur in childhood or adolescence. Mulvihill-Smith syndrome has been reported in only four individuals in the medical literature.Storm syndrome (Werner-like syndrome) is an extremely rare inherited disorder associated with premature aging and heart disease. Other symptoms during adolescence may include the loss of eyebrows and eyelashes, and the thinning and graying of scalp hair. The skin over the hands and face becomes tight with a wrinkled appearance. Some affected individuals also have pain and impairment of joint function.Combined defect of growth factors (Werner-like syndrome due to combined growth factor deficiency) is an extremely rare inherited disorder. The symptoms of this disorder are similar to those of Werner syndrome and include the loss of the fatty layers on the arms and legs, a beak-like nose, a small jaw, and/or a narrow mouth. Other symptoms may include impaired joint function, flat feet, and thin, tight skin.Rothmund-Thomson syndrome is an inherited skin disorder characterized by abnormal redness of the skin caused by congested and obstructed small blood vessels (capillaries). Eventually the capillaries may become obstructed. Most people with Rothmund-Thomson syndrome have small stature, loss of muscle and red coloring of the skin. Some people are abnormally sensitive to light (photosensitivity) and may develop cataracts during adolescence. Other symptoms may include underdeveloped teeth and nails, unusually small hands and feet, malformed or missing thumbs and/or sparse and prematurely gray hair or baldness. (For more information on this disorder, choose “Rothmund-Thomson” as your search term in the Rare Disease Database.)
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Diagnosis of Werner Syndrome
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In some people, Werner syndrome may be recognized clinically as early as approximately age 15, based upon a thorough clinical evaluation, characteristic physical findings (e.g., absence of growth spurt at puberty, short stature, low weight), and a careful patient and family history. However, the disorder often may not be recognized or confirmed until the third or fourth decades of life, once certain distinctive symptoms and findings are noted (e.g., premature graying and hair loss, distinctive voice, loss of subcutaneous tissue, muscular atrophy, skin changes, bilateral senile cataracts, etc.).Specialized imaging studies and laboratory tests may be conducted to detect, confirm, or characterize certain abnormalities potentially associated with the disorder. For example, eye specialists (ophthalmologists) may regularly monitor affected individuals for the development of cataracts with certain measures, such as use of a specialized instrument that enables visualization of the inside of the eyes (ophthalmoscope). If cataracts are detected, an illuminated microscope (slit lamp) may be used to examine the internal structures of the front regions of the eyes, enabling ophthalmologists to determine the specific location and extent of the cataracts.Diagnostic testing may include monitoring of blood sugar levels to ensure prompt detection of diabetes mellitus, bone scans and blood tests for osteoporosis and/or other studies. In addition, thorough cardiac evaluations and ongoing monitoring may also be performed (e.g., clinical examinations, X-ray studies, specialized cardiac tests) to assess associated cardiovascular abnormalities and determine appropriate disease management. Individuals with Werner syndrome should also be regularly monitored as necessary to ensure the prompt detection and appropriate treatment of certain malignancies or benign tumors that may occur in association with the disorder (e.g., osteosarcoma, meningioma).In some people, specialized laboratory tests may be performed on cultured skin cells (fibroblasts) from affected individuals, demonstrating abnormally decreased replication of Werner syndrome fibroblasts. Evaluation of the chromosomal make-up (karyotype) within the nuclei of cultured fibroblasts and certain white blood cells (lymphocytes) may reveal a high frequency of certain chromosomal rearrangements (variegated translocation mosaicism). (For more information, please see the “Causes” section of this report above.) In addition, according to several investigators, urine tests may reveal elevated levels of hyaluronic acid, a complex carbohydrate that is present in the spaces between certain cells (intercellular spaces) within certain connective tissues. The implications of this finding are not understood.Confirmation of a clinical diagnosis of Werner syndrome may be achieved through molecular testing of the WRN gene. Molecular sequencing of the WRN gene to detect disease-causing variants, as well as biochemical testing to quantitate the amount of WRN protein produced by cells, is available on a clinical basis.
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Diagnosis of Werner Syndrome. In some people, Werner syndrome may be recognized clinically as early as approximately age 15, based upon a thorough clinical evaluation, characteristic physical findings (e.g., absence of growth spurt at puberty, short stature, low weight), and a careful patient and family history. However, the disorder often may not be recognized or confirmed until the third or fourth decades of life, once certain distinctive symptoms and findings are noted (e.g., premature graying and hair loss, distinctive voice, loss of subcutaneous tissue, muscular atrophy, skin changes, bilateral senile cataracts, etc.).Specialized imaging studies and laboratory tests may be conducted to detect, confirm, or characterize certain abnormalities potentially associated with the disorder. For example, eye specialists (ophthalmologists) may regularly monitor affected individuals for the development of cataracts with certain measures, such as use of a specialized instrument that enables visualization of the inside of the eyes (ophthalmoscope). If cataracts are detected, an illuminated microscope (slit lamp) may be used to examine the internal structures of the front regions of the eyes, enabling ophthalmologists to determine the specific location and extent of the cataracts.Diagnostic testing may include monitoring of blood sugar levels to ensure prompt detection of diabetes mellitus, bone scans and blood tests for osteoporosis and/or other studies. In addition, thorough cardiac evaluations and ongoing monitoring may also be performed (e.g., clinical examinations, X-ray studies, specialized cardiac tests) to assess associated cardiovascular abnormalities and determine appropriate disease management. Individuals with Werner syndrome should also be regularly monitored as necessary to ensure the prompt detection and appropriate treatment of certain malignancies or benign tumors that may occur in association with the disorder (e.g., osteosarcoma, meningioma).In some people, specialized laboratory tests may be performed on cultured skin cells (fibroblasts) from affected individuals, demonstrating abnormally decreased replication of Werner syndrome fibroblasts. Evaluation of the chromosomal make-up (karyotype) within the nuclei of cultured fibroblasts and certain white blood cells (lymphocytes) may reveal a high frequency of certain chromosomal rearrangements (variegated translocation mosaicism). (For more information, please see the “Causes” section of this report above.) In addition, according to several investigators, urine tests may reveal elevated levels of hyaluronic acid, a complex carbohydrate that is present in the spaces between certain cells (intercellular spaces) within certain connective tissues. The implications of this finding are not understood.Confirmation of a clinical diagnosis of Werner syndrome may be achieved through molecular testing of the WRN gene. Molecular sequencing of the WRN gene to detect disease-causing variants, as well as biochemical testing to quantitate the amount of WRN protein produced by cells, is available on a clinical basis.
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Therapies of Werner Syndrome
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TreatmentThe treatment of Werner syndrome is directed toward the specific symptoms that are apparent in each individual. Disorder management may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected individual’s treatment. Such specialists may include internists; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and other related tissues (orthopedists); physicians who diagnose and treat abnormalities of the heart and its major blood vessels; eye specialists (ophthalmologists); physicians who diagnose and treat disorders of the endocrine system (endocrinologists); and/or other health care professionals.Specific therapies for individuals with Werner syndrome are symptomatic and supportive. According to reports in the medical literature, diabetes mellitus is typically mild and may often be managed with dietary changes and appropriate medications by mouth to decrease elevated sugar (glucose) levels in the blood (oral hypoglycemic medications).In affected individuals with cataracts, treatment may include surgical removal of the clouded lens and implantation of a substitute lens (intraocular lens) or prescription of corrective glasses or contact lenses. Some physicians report that individuals with Werner syndrome may have a significantly increased risk of separation of surgical wound layers (wound dehiscence) and/or other complications (e.g., corneal endothelial decompensation). Therefore, these physicians recommend that special precautions be taken during such surgical procedures (e.g., small surgical incisions, avoidance of local or systemic cortisone).In individuals with Werner syndrome, measures to manage arteriosclerosis and associated cardiovascular abnormalities are symptomatic and supportive. For example, in those with episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks), treatment may include the use of certain medications that may help to minimize or manage such symptoms.If benign or malignant tumors develop in association with Werner syndrome, appropriate treatment measures may vary depending upon the specific tumor type present; whether the tumor is benign or malignant; stage, grade and/or extent of disease; and/or other factors. Depending upon such factors, treatment methods may include surgery, use of certain anticancer drugs (chemotherapy), radiation therapy and/or other measures.Genetic counseling is recommended for individuals with Werner syndrome and their families.
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Therapies of Werner Syndrome. TreatmentThe treatment of Werner syndrome is directed toward the specific symptoms that are apparent in each individual. Disorder management may require the coordinated efforts of a team of specialists who may need to systematically and comprehensively plan an affected individual’s treatment. Such specialists may include internists; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and other related tissues (orthopedists); physicians who diagnose and treat abnormalities of the heart and its major blood vessels; eye specialists (ophthalmologists); physicians who diagnose and treat disorders of the endocrine system (endocrinologists); and/or other health care professionals.Specific therapies for individuals with Werner syndrome are symptomatic and supportive. According to reports in the medical literature, diabetes mellitus is typically mild and may often be managed with dietary changes and appropriate medications by mouth to decrease elevated sugar (glucose) levels in the blood (oral hypoglycemic medications).In affected individuals with cataracts, treatment may include surgical removal of the clouded lens and implantation of a substitute lens (intraocular lens) or prescription of corrective glasses or contact lenses. Some physicians report that individuals with Werner syndrome may have a significantly increased risk of separation of surgical wound layers (wound dehiscence) and/or other complications (e.g., corneal endothelial decompensation). Therefore, these physicians recommend that special precautions be taken during such surgical procedures (e.g., small surgical incisions, avoidance of local or systemic cortisone).In individuals with Werner syndrome, measures to manage arteriosclerosis and associated cardiovascular abnormalities are symptomatic and supportive. For example, in those with episodes of chest pain due to deficient oxygen supply to heart muscle (anginal attacks), treatment may include the use of certain medications that may help to minimize or manage such symptoms.If benign or malignant tumors develop in association with Werner syndrome, appropriate treatment measures may vary depending upon the specific tumor type present; whether the tumor is benign or malignant; stage, grade and/or extent of disease; and/or other factors. Depending upon such factors, treatment methods may include surgery, use of certain anticancer drugs (chemotherapy), radiation therapy and/or other measures.Genetic counseling is recommended for individuals with Werner syndrome and their families.
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Overview of Wernicke-Korsakoff Syndrome
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Wernicke syndrome and Korsakoff syndrome (WKS) are distinct but overlapping disorders that occur due to a deficiency of thiamine (vitamin B1). Wernicke syndrome, also known as Wernicke encephalopathy, is a neurological disease characterized by three main clinical symptoms: confusion, the inability to coordinate voluntary movement (ataxia) and eye (ocular) abnormalities. Wernicke syndrome is considered the acute phase of WKS and if left untreated, transitions to the chronic irreversible Korsakoff syndrome. When these two disorders occur together, the term Wernicke-Korsakoff syndrome is used. In the United States, most cases occur associated with chronic consumption of alcohol but can occur in individuals who have malnutrition, eating disorders or other conditions that cause a deficiency in thiamine. Additionally, studies indicate that there may be some genetic predisposition for the disease.
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Overview of Wernicke-Korsakoff Syndrome. Wernicke syndrome and Korsakoff syndrome (WKS) are distinct but overlapping disorders that occur due to a deficiency of thiamine (vitamin B1). Wernicke syndrome, also known as Wernicke encephalopathy, is a neurological disease characterized by three main clinical symptoms: confusion, the inability to coordinate voluntary movement (ataxia) and eye (ocular) abnormalities. Wernicke syndrome is considered the acute phase of WKS and if left untreated, transitions to the chronic irreversible Korsakoff syndrome. When these two disorders occur together, the term Wernicke-Korsakoff syndrome is used. In the United States, most cases occur associated with chronic consumption of alcohol but can occur in individuals who have malnutrition, eating disorders or other conditions that cause a deficiency in thiamine. Additionally, studies indicate that there may be some genetic predisposition for the disease.
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Symptoms of Wernicke-Korsakoff Syndrome
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WKS is the result of thiamine deficiency that leads to acute symptoms (Wernicke syndrome) that if left untreated lead to the chronic irreversible Korsakoff syndrome. Patients that experience an overlap of symptoms from both are diagnosed with WKS.Wernicke syndrome is characterized by three main clinical symptoms: mental status changes (e.g., confused state), the inability to coordinate voluntary movement (ataxia) and eye abnormalities. Affected individuals may not display all three symptoms.Confusion and disorientation associated with Wernicke syndrome develops over a few days or weeks and is the main problem associated with the disorder. It is an acute syndrome precipitated by thiamine deficiency. Affected individuals may experience lethargy, inattentiveness, drowsiness and indifference. Delirium often occurs especially in alcoholic patients who are also withdrawing from alcohol. If left untreated, affected individuals may develop stupor or loss of consciousness (coma). Some affected individuals may have a slow, unsteady gait. In the acute stage of the disease, this may prevent an affected individual from standing or walking without assistance.Ocular abnormalities associated with Wernicke syndrome include double vision, rapid, involuntary eye movements (nystagmus), paralysis of certain eye muscles (ophthalmoplegia) and rarely, drooping of the upper eyelids (ptosis).Approximately 80-90 percent of individuals with Wernicke syndrome develop Korsakoff syndrome. The symptoms of Korsakoff syndrome often develop as the mental symptoms of Wernicke syndrome begin to lessen.Korsakoff syndrome is characterized by memory impairment, specifically short-term memory loss (i.e., the inability to form new memories or retain new information). Some affected individuals may also have random loss of long-term memories. Rarely, individuals may create imaginary events to fill in gaps in their memory (confabulation).Attention and social behavior are relatively preserved. Affected people are able to carry on a socially appropriate conversation that may seem normal. People with Korsakoff syndrome are usually unaware of their illness.WKS may be long lasting or permanent and affects many nerves (polyneuropathy), especially those outside of the central nervous system (peripheral neuropathy). Peripheral neuropathy may cause weakness of the arms and legs and contribute to difficulty walking. A variety of cardiovascular abnormalities may also occur in individuals with WKS including a rapid heartbeat (tachycardia), low blood pressure upon standing (postural hypotension) and loss of consciousness (syncope). Hypothermia (body losing heat too quickly) can also be a symptom of WKS.Other symptoms can include weakness in limbs, poor muscle coordination, unsteady gait, slow walking, rapid eye movements, paralysis of eye muscles, poor fine motor function and decreased sense of smell.Advanced stages of the acute phase of WKS lead to coma and death in 10-20% of patients.
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Symptoms of Wernicke-Korsakoff Syndrome. WKS is the result of thiamine deficiency that leads to acute symptoms (Wernicke syndrome) that if left untreated lead to the chronic irreversible Korsakoff syndrome. Patients that experience an overlap of symptoms from both are diagnosed with WKS.Wernicke syndrome is characterized by three main clinical symptoms: mental status changes (e.g., confused state), the inability to coordinate voluntary movement (ataxia) and eye abnormalities. Affected individuals may not display all three symptoms.Confusion and disorientation associated with Wernicke syndrome develops over a few days or weeks and is the main problem associated with the disorder. It is an acute syndrome precipitated by thiamine deficiency. Affected individuals may experience lethargy, inattentiveness, drowsiness and indifference. Delirium often occurs especially in alcoholic patients who are also withdrawing from alcohol. If left untreated, affected individuals may develop stupor or loss of consciousness (coma). Some affected individuals may have a slow, unsteady gait. In the acute stage of the disease, this may prevent an affected individual from standing or walking without assistance.Ocular abnormalities associated with Wernicke syndrome include double vision, rapid, involuntary eye movements (nystagmus), paralysis of certain eye muscles (ophthalmoplegia) and rarely, drooping of the upper eyelids (ptosis).Approximately 80-90 percent of individuals with Wernicke syndrome develop Korsakoff syndrome. The symptoms of Korsakoff syndrome often develop as the mental symptoms of Wernicke syndrome begin to lessen.Korsakoff syndrome is characterized by memory impairment, specifically short-term memory loss (i.e., the inability to form new memories or retain new information). Some affected individuals may also have random loss of long-term memories. Rarely, individuals may create imaginary events to fill in gaps in their memory (confabulation).Attention and social behavior are relatively preserved. Affected people are able to carry on a socially appropriate conversation that may seem normal. People with Korsakoff syndrome are usually unaware of their illness.WKS may be long lasting or permanent and affects many nerves (polyneuropathy), especially those outside of the central nervous system (peripheral neuropathy). Peripheral neuropathy may cause weakness of the arms and legs and contribute to difficulty walking. A variety of cardiovascular abnormalities may also occur in individuals with WKS including a rapid heartbeat (tachycardia), low blood pressure upon standing (postural hypotension) and loss of consciousness (syncope). Hypothermia (body losing heat too quickly) can also be a symptom of WKS.Other symptoms can include weakness in limbs, poor muscle coordination, unsteady gait, slow walking, rapid eye movements, paralysis of eye muscles, poor fine motor function and decreased sense of smell.Advanced stages of the acute phase of WKS lead to coma and death in 10-20% of patients.
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Causes of Wernicke-Korsakoff Syndrome
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WKS is caused by a deficiency of thiamine (vitamin B1). Thiamine is an important nutrient required to metabolize glucose used by the brain for energy. The lack of thiamine affects brain functions in the most metabolically active brain regions, including the activity of the hypothalamus which regulates temperature, appetite, emotions and growth. Thiamine deficiency affects the cells of the nervous and cardiovascular systems to a greater degree than the cells of other organ systems.In the United States, most cases of WKS occur in alcoholics. Alcohol reduces the absorption of thiamine by the body, diminishes stores of thiamine in the liver and hampers the activity of the enzyme that converts thiamine into an active state.The disorder may also occur due to malnutrition. Causes of malnutrition that may result in WKS include starvation, eating disorders (e.g., anorexia), prolonged or chronic vomiting as found in certain disorders such as hyperemesis gravidarum (vomiting of pregnancy). In addition, chronic disorders such as cancer, AIDS, disorders of the stomach (gastropathies) and kidney disorders may also cause WKS.Hereditary factors may cause some individuals to have a genetic predisposition to developing WKS. Variants in the high affinity thiamine transporter gene have been implicated. The SLC19A2 gene provides instructions for making a protein called thiamine transporter 1. This protein is located on the surface of cells, where it works to bring vitamin B1 (thiamine) into cells. More research is necessary to determine what role genetics plays in the development of the disorder.
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Causes of Wernicke-Korsakoff Syndrome. WKS is caused by a deficiency of thiamine (vitamin B1). Thiamine is an important nutrient required to metabolize glucose used by the brain for energy. The lack of thiamine affects brain functions in the most metabolically active brain regions, including the activity of the hypothalamus which regulates temperature, appetite, emotions and growth. Thiamine deficiency affects the cells of the nervous and cardiovascular systems to a greater degree than the cells of other organ systems.In the United States, most cases of WKS occur in alcoholics. Alcohol reduces the absorption of thiamine by the body, diminishes stores of thiamine in the liver and hampers the activity of the enzyme that converts thiamine into an active state.The disorder may also occur due to malnutrition. Causes of malnutrition that may result in WKS include starvation, eating disorders (e.g., anorexia), prolonged or chronic vomiting as found in certain disorders such as hyperemesis gravidarum (vomiting of pregnancy). In addition, chronic disorders such as cancer, AIDS, disorders of the stomach (gastropathies) and kidney disorders may also cause WKS.Hereditary factors may cause some individuals to have a genetic predisposition to developing WKS. Variants in the high affinity thiamine transporter gene have been implicated. The SLC19A2 gene provides instructions for making a protein called thiamine transporter 1. This protein is located on the surface of cells, where it works to bring vitamin B1 (thiamine) into cells. More research is necessary to determine what role genetics plays in the development of the disorder.
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Affects of Wernicke-Korsakoff Syndrome
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WKS occurs in 1-2 percent of the general population in the United States. The disorder affects slightly more males than females and is evenly distributed between ages 30-70. Certain subpopulations such as the homeless, elderly living in isolation and psychiatric patients have higher prevalence rates.
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Affects of Wernicke-Korsakoff Syndrome. WKS occurs in 1-2 percent of the general population in the United States. The disorder affects slightly more males than females and is evenly distributed between ages 30-70. Certain subpopulations such as the homeless, elderly living in isolation and psychiatric patients have higher prevalence rates.
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Related disorders of Wernicke-Korsakoff Syndrome
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Symptoms of the following disorder can be similar to those of Wernicke-Korsakoff syndrome. Comparisons may be useful for a differential diagnosis:Leigh syndrome is a rapidly progressive neurological disorder that begins between 3 months to 2 years. Another form of this disease occurs during adolescence into early adulthood and is called the adult-onset form of Leigh syndrome. Visual disturbances are generally the early symptoms followed by progressive difficulty coordinating voluntary movements (ataxia), sudden muscle spasms, seizures and varying degrees of dementia. The adult onset form of Leigh syndrome is rare and progresses slower than the classic form of the disease. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database).Additional diseases to consider in differential diagnosis:
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Related disorders of Wernicke-Korsakoff Syndrome. Symptoms of the following disorder can be similar to those of Wernicke-Korsakoff syndrome. Comparisons may be useful for a differential diagnosis:Leigh syndrome is a rapidly progressive neurological disorder that begins between 3 months to 2 years. Another form of this disease occurs during adolescence into early adulthood and is called the adult-onset form of Leigh syndrome. Visual disturbances are generally the early symptoms followed by progressive difficulty coordinating voluntary movements (ataxia), sudden muscle spasms, seizures and varying degrees of dementia. The adult onset form of Leigh syndrome is rare and progresses slower than the classic form of the disease. (For more information on this disorder, choose “Leigh” as your search term in the Rare Disease Database).Additional diseases to consider in differential diagnosis:
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Diagnosis of Wernicke-Korsakoff Syndrome
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A diagnosis of WKS is made based upon a thorough clinical evaluation and a detailed patient history. This includes obtaining a person’s nutrition and daily drinking habits and current and past behaviors to identify if there has been a long-term abuse of alcohol. Tests such as routine laboratory screens and liver function tests can rule out other disorders with similar presentations. Tests that measure thiamine and erythrocyte transketolase acitivity (both which are reduced in WKS) may also help in attaining a diagnosis. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be necessary to rule out tumors, infarcts and bleeding (hemorrhaging). CT scans and MRIs may also reveal brain changes that are indicative of WKS (e.g., shrunken mammillary bodies, enlarged ventricles). The mammillary bodies are a pair of small round structures found within the brain that form part of the limbic system. The limbic system is a group of structures within the brain that are involved with emotions and in the formation of memory.
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Diagnosis of Wernicke-Korsakoff Syndrome. A diagnosis of WKS is made based upon a thorough clinical evaluation and a detailed patient history. This includes obtaining a person’s nutrition and daily drinking habits and current and past behaviors to identify if there has been a long-term abuse of alcohol. Tests such as routine laboratory screens and liver function tests can rule out other disorders with similar presentations. Tests that measure thiamine and erythrocyte transketolase acitivity (both which are reduced in WKS) may also help in attaining a diagnosis. Computed tomography (CT) scanning and magnetic resonance imaging (MRI) may be necessary to rule out tumors, infarcts and bleeding (hemorrhaging). CT scans and MRIs may also reveal brain changes that are indicative of WKS (e.g., shrunken mammillary bodies, enlarged ventricles). The mammillary bodies are a pair of small round structures found within the brain that form part of the limbic system. The limbic system is a group of structures within the brain that are involved with emotions and in the formation of memory.
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Therapies of Wernicke-Korsakoff Syndrome
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Treatment
The immediate administration of thiamine (replacement therapy) is used to treat individuals with WKS. Thiamine is given intravenously because abdominal absorption can be hampered in affected individuals. Mental status changes, vision abnormalities and ataxia all usually improve upon administration of thiamine. Thiamine administration may continue daily for several months. With early treatment, Wernicke syndrome will not necessarily progress to WKS.Abstinence from alcohol and proper dietary changes are recommended. Magnesium and potassium are often low in people with WKS. These and other electrolytes may need to be supplemented in addition to the thiamine. Chronically malnourished patients should receive supplementation of all B vitamins until normal intake resumes. A multidisciplinary team may be required depending upon patient’s level of recovery. Specialists in neurology, psychiatry (mental health), ophthalmology (eye doctor), cardiology (heart) and gastroenterology (stomach and bowel issues) may be needed to manage patient symptoms. In addition, some affected individuals may benefit from psychological methods designed to treat mental and emotional disorders (psychotherapy).The challenges that patients face with movement and gait can be treated with physical therapy. The walking difficulties may be permanent depending on the initial loss of movement and the timeliness of therapy.If the disorder is caught early and treatment started promptly a full or significant recovery can be made. In some patients, confusion and mental problems may take months to resolve. In severe cases, brain damage may cause lasting problems with memory and gait. Despite early intervention, patients with WKS may not fully recover and can require long term rehabilitation and support.Other treatment is symptomatic and supportive.
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Therapies of Wernicke-Korsakoff Syndrome. Treatment
The immediate administration of thiamine (replacement therapy) is used to treat individuals with WKS. Thiamine is given intravenously because abdominal absorption can be hampered in affected individuals. Mental status changes, vision abnormalities and ataxia all usually improve upon administration of thiamine. Thiamine administration may continue daily for several months. With early treatment, Wernicke syndrome will not necessarily progress to WKS.Abstinence from alcohol and proper dietary changes are recommended. Magnesium and potassium are often low in people with WKS. These and other electrolytes may need to be supplemented in addition to the thiamine. Chronically malnourished patients should receive supplementation of all B vitamins until normal intake resumes. A multidisciplinary team may be required depending upon patient’s level of recovery. Specialists in neurology, psychiatry (mental health), ophthalmology (eye doctor), cardiology (heart) and gastroenterology (stomach and bowel issues) may be needed to manage patient symptoms. In addition, some affected individuals may benefit from psychological methods designed to treat mental and emotional disorders (psychotherapy).The challenges that patients face with movement and gait can be treated with physical therapy. The walking difficulties may be permanent depending on the initial loss of movement and the timeliness of therapy.If the disorder is caught early and treatment started promptly a full or significant recovery can be made. In some patients, confusion and mental problems may take months to resolve. In severe cases, brain damage may cause lasting problems with memory and gait. Despite early intervention, patients with WKS may not fully recover and can require long term rehabilitation and support.Other treatment is symptomatic and supportive.
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Overview of West Nile Encephalitis
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There are seventeen species of birds that are the known carriers of and transmit West Nile Encephalitis (WNE) to humans via the Culex, Aedes, and Anopheles mosquitoes. WNE first causes symptomatic or asymptomatic illness in wild migratory birds that act as viral replication factories. Wild birds infected with WNE contain high titers of the virus and remain viremic for 1-2 weeks, making them ideal hosts to perpetuate the disease. Mosquitoes transmit WNE from birds to humans. Horses, dogs, and other small animals may harbor WNE after being bitten; however, they are inefficient transmitters because viral titers are relatively low, and WNE viremia is short-lived in these animals.
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Overview of West Nile Encephalitis. There are seventeen species of birds that are the known carriers of and transmit West Nile Encephalitis (WNE) to humans via the Culex, Aedes, and Anopheles mosquitoes. WNE first causes symptomatic or asymptomatic illness in wild migratory birds that act as viral replication factories. Wild birds infected with WNE contain high titers of the virus and remain viremic for 1-2 weeks, making them ideal hosts to perpetuate the disease. Mosquitoes transmit WNE from birds to humans. Horses, dogs, and other small animals may harbor WNE after being bitten; however, they are inefficient transmitters because viral titers are relatively low, and WNE viremia is short-lived in these animals.
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Symptoms of West Nile Encephalitis
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Patients with WNE may present with a wide range of severity in symptoms and may features of encephalitis, aseptic meningitis (meningoencephalitis), or both. It is common for patients to have a mild febrile illness accompanied by headache, mental confusion, tremors, or flaccid paralysis. Symptoms are most obvious in people who are very young and people who are elderly. Many people who are infected (at least most children) are also often asymptomatic or have a nonspecific flu-like illness. A minority of people may develop neurologic disease.The extent and severity of viral invasion of the central nervous system (CNS) determine the clinical expression of WNE. Most patients are febrile or have low-grade fevers. Patients presenting with encephalitis have mental confusion or disorientation and may have decreased consciousness. Patients with severe cases of WNE may present with stupor or coma. The most common ophthalmic manifestation for WNE is chorioretinitis and about 10% of patients have an enlarged liver and spelnomegaly. CNS findings include a stiff neck with meningeal signs, including positive Kernig or Brudzinski signs in patients with aseptic meningitis or meningoencephalitis. Generalized adenopathy and an enlarged submental node are also very common.
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Symptoms of West Nile Encephalitis. Patients with WNE may present with a wide range of severity in symptoms and may features of encephalitis, aseptic meningitis (meningoencephalitis), or both. It is common for patients to have a mild febrile illness accompanied by headache, mental confusion, tremors, or flaccid paralysis. Symptoms are most obvious in people who are very young and people who are elderly. Many people who are infected (at least most children) are also often asymptomatic or have a nonspecific flu-like illness. A minority of people may develop neurologic disease.The extent and severity of viral invasion of the central nervous system (CNS) determine the clinical expression of WNE. Most patients are febrile or have low-grade fevers. Patients presenting with encephalitis have mental confusion or disorientation and may have decreased consciousness. Patients with severe cases of WNE may present with stupor or coma. The most common ophthalmic manifestation for WNE is chorioretinitis and about 10% of patients have an enlarged liver and spelnomegaly. CNS findings include a stiff neck with meningeal signs, including positive Kernig or Brudzinski signs in patients with aseptic meningitis or meningoencephalitis. Generalized adenopathy and an enlarged submental node are also very common.
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Causes of West Nile Encephalitis
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Mosquito bites are the main culprits for the spread of WNE with an incubation period of WNE is 1-6 day but many patients may not provide a mosquito bite history. WNE usually occurs in the summer when mosquitoes, wild migratory birds, and humans are in close proximity outdoors. Mosquito bites, which are particularly prone to occur during feeding times (dawn and dusk) in the summer months, transmit WNE and prolonged contact or multiple mosquito bites enhances risk. WNE may be transmitted in organ transplants and WNE virus has been found in breast milk.WNE, as with other arthropod-borne viral encephalitis, traverses the blood-brain barrier and infects the brain parenchyma, clinically manifesting as viral encephalitis. WNE may also affect the leptomeninges, resulting in a clinical presentation of aseptic meningitis (viral meningitis). Patients with WNE may present with features of both encephalitis and aseptic meningitis (meningoencephalitis).
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Causes of West Nile Encephalitis. Mosquito bites are the main culprits for the spread of WNE with an incubation period of WNE is 1-6 day but many patients may not provide a mosquito bite history. WNE usually occurs in the summer when mosquitoes, wild migratory birds, and humans are in close proximity outdoors. Mosquito bites, which are particularly prone to occur during feeding times (dawn and dusk) in the summer months, transmit WNE and prolonged contact or multiple mosquito bites enhances risk. WNE may be transmitted in organ transplants and WNE virus has been found in breast milk.WNE, as with other arthropod-borne viral encephalitis, traverses the blood-brain barrier and infects the brain parenchyma, clinically manifesting as viral encephalitis. WNE may also affect the leptomeninges, resulting in a clinical presentation of aseptic meningitis (viral meningitis). Patients with WNE may present with features of both encephalitis and aseptic meningitis (meningoencephalitis).
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Affects of West Nile Encephalitis
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In the US the initial cases of WNE were first identified in the greater New York area, but cases have now occurred in western states. Wild birds with WNE virus have also been identified in parts of Canada. WNE is common in the Middle East, Asia, and Africa WNE seropositivity of children in Egypt is approximately 50%. WNE is the most common cause of viral aseptic meningitis or encephalitis in patients presenting to emergency departments in Cairo. Both sexes are affected equally and it is more frequent in elderly patients.
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Affects of West Nile Encephalitis. In the US the initial cases of WNE were first identified in the greater New York area, but cases have now occurred in western states. Wild birds with WNE virus have also been identified in parts of Canada. WNE is common in the Middle East, Asia, and Africa WNE seropositivity of children in Egypt is approximately 50%. WNE is the most common cause of viral aseptic meningitis or encephalitis in patients presenting to emergency departments in Cairo. Both sexes are affected equally and it is more frequent in elderly patients.
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Related disorders of West Nile Encephalitis
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Encephalopathy is a feature of many systemic illnesses that presents with encephalitis. Most of these patients have extra-CNS findings that suggest the underlying disease process. Common disorders with CNS manifestations that may mimic WNE include subacute bacterial endocarditis, Legionnaires Disease, Rocky Mountain Spotted Fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus 6, and systemic lupus erythematosus cerebritis.Enteroviral aseptic meningitisThe most common cause of aseptic meningitis encountered during the summer months is enteroviral meningitis. Enteroviral aseptic meningitis is most commonly due to coxsackieviruses but may also be due to enterocytopathogenic human orphan virus or nonparalytic strains of poliovirus. Enteroviral meningitis may occur after water exposure in swimming pools, lakes, streams, or oceans as well as after contact with infected individuals.Acute enteroviral CNS infections usually manifest as aseptic meningitis, uncommonly as meningoencephalitis, or rarely as encephalitis. Nonexudative pharyngitis, maculopapular extremity rash, loose stools, and even diarrhea often accompany enteroviral aseptic meningitis, which provides clues to its presence.Enteroviral meningitis is not accompanied by paralysis or prolonged and/or profound lymphopenia.
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Related disorders of West Nile Encephalitis. Encephalopathy is a feature of many systemic illnesses that presents with encephalitis. Most of these patients have extra-CNS findings that suggest the underlying disease process. Common disorders with CNS manifestations that may mimic WNE include subacute bacterial endocarditis, Legionnaires Disease, Rocky Mountain Spotted Fever, Epstein-Barr virus infectious mononucleosis, human herpesvirus 6, and systemic lupus erythematosus cerebritis.Enteroviral aseptic meningitisThe most common cause of aseptic meningitis encountered during the summer months is enteroviral meningitis. Enteroviral aseptic meningitis is most commonly due to coxsackieviruses but may also be due to enterocytopathogenic human orphan virus or nonparalytic strains of poliovirus. Enteroviral meningitis may occur after water exposure in swimming pools, lakes, streams, or oceans as well as after contact with infected individuals.Acute enteroviral CNS infections usually manifest as aseptic meningitis, uncommonly as meningoencephalitis, or rarely as encephalitis. Nonexudative pharyngitis, maculopapular extremity rash, loose stools, and even diarrhea often accompany enteroviral aseptic meningitis, which provides clues to its presence.Enteroviral meningitis is not accompanied by paralysis or prolonged and/or profound lymphopenia.
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Diagnosis of West Nile Encephalitis
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Electroencephalogram: This is the most sensitive way to make a presumptive diagnosis of HSV-1 encephalitis. An abnormal temporal lobe focus is present on EEG as early as the first few days of the disease.EEG shows unilateral focal electrical abnormalities in the temporal lobe.Lumbar puncture: CSF reveals mild-to-moderate pleocytosis with a lymphocytic predominance in WNE. CSF protein is variably elevated, and the CSF glucose level is not decreased.The CSF lactic acid level is not elevated, and RBCs, excluding traumatic taps, are not present in WNE. CSF Gram stain and bacterial culture findings are negative.
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Diagnosis of West Nile Encephalitis. Electroencephalogram: This is the most sensitive way to make a presumptive diagnosis of HSV-1 encephalitis. An abnormal temporal lobe focus is present on EEG as early as the first few days of the disease.EEG shows unilateral focal electrical abnormalities in the temporal lobe.Lumbar puncture: CSF reveals mild-to-moderate pleocytosis with a lymphocytic predominance in WNE. CSF protein is variably elevated, and the CSF glucose level is not decreased.The CSF lactic acid level is not elevated, and RBCs, excluding traumatic taps, are not present in WNE. CSF Gram stain and bacterial culture findings are negative.
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Therapies of West Nile Encephalitis
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Medical CareProvide supportive care to minimize the potential for cerebral edema. In comatose patients, pay special attention to maintaining a clear airway. Fluid replacement is also essential.Surgical CareNo surgical care is necessary.
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Therapies of West Nile Encephalitis. Medical CareProvide supportive care to minimize the potential for cerebral edema. In comatose patients, pay special attention to maintaining a clear airway. Fluid replacement is also essential.Surgical CareNo surgical care is necessary.
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Overview of West Syndrome
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West syndrome is a constellation of symptoms characterized by epileptic/infantile spasms, abnormal brain wave patterns called hypsarrhythmia and intellectual disability. The spasms that occur may range from violent jackknife or “salaam” movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. They can also occur in older patients; if this happens, they are called “epileptic spasms” rather than infantile spasms. Currently, the International League Against Epilepsy (ILAE) has revised the terminology and epileptic spasms is now preferentially used to encompass the different age groups of onset. There are many different causes of epileptic spasms and if a specific cause can be identified, a diagnosis of symptomatic epileptic spasms can be made. If a cause cannot be determined, a diagnosis of cryptogenic epileptic spasms is made.
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Overview of West Syndrome. West syndrome is a constellation of symptoms characterized by epileptic/infantile spasms, abnormal brain wave patterns called hypsarrhythmia and intellectual disability. The spasms that occur may range from violent jackknife or “salaam” movements where the whole body bends in half, or they may be no more than a mild twitching of the shoulder or eye changes. These spasms usually begin in the early months after birth and can sometimes be helped with medication. They can also occur in older patients; if this happens, they are called “epileptic spasms” rather than infantile spasms. Currently, the International League Against Epilepsy (ILAE) has revised the terminology and epileptic spasms is now preferentially used to encompass the different age groups of onset. There are many different causes of epileptic spasms and if a specific cause can be identified, a diagnosis of symptomatic epileptic spasms can be made. If a cause cannot be determined, a diagnosis of cryptogenic epileptic spasms is made.
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Symptoms of West Syndrome
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Symptoms associated with West syndrome usually begin during the first year of life. The average age of onset for epileptic spasms is at 6 months. Epileptic spasms are characterized by involuntary muscle spasms that occur due to episodes of uncontrolled electrical disturbances in the brain (seizures). Each involuntary spasm typically begins suddenly and lasts for only a few seconds and occurs usually in clusters that can last over 10-20 minutes. Such episodes, which may occur upon awakening or after feeding, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.Infants with West syndrome also have very abnormal electroencephalogram (EEG) with high amplitude, chaotic spike wave patterns (hypsarrhythmia). Most children will have regression of skills or delays in acquiring skills that require coordination of muscles and voluntary movements (psychomotor retardation).Approximately a third of children with West syndrome may develop recurrent epileptic seizures as they age. The syndrome often develops into Lennox-Gastaut syndrome with mixed types of seizures that are difficult to control and is associated with intellectual disability. (For more information on Lennox-Gastaut syndrome, see the Related Disorders section below.). Approximately another third of children with West syndrome will continue to have epileptic spasms at an older age . The last third to quarter of patients will have spasms that resolve with time, usually in patients who have no clear etiology.
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Symptoms of West Syndrome. Symptoms associated with West syndrome usually begin during the first year of life. The average age of onset for epileptic spasms is at 6 months. Epileptic spasms are characterized by involuntary muscle spasms that occur due to episodes of uncontrolled electrical disturbances in the brain (seizures). Each involuntary spasm typically begins suddenly and lasts for only a few seconds and occurs usually in clusters that can last over 10-20 minutes. Such episodes, which may occur upon awakening or after feeding, are characterized by sudden, involuntary contractions of the head, neck, and trunk and/or uncontrolled extension of the legs and/or arms. The duration, intensity, and muscle groups affected by seizures vary from infant to infant.Infants with West syndrome also have very abnormal electroencephalogram (EEG) with high amplitude, chaotic spike wave patterns (hypsarrhythmia). Most children will have regression of skills or delays in acquiring skills that require coordination of muscles and voluntary movements (psychomotor retardation).Approximately a third of children with West syndrome may develop recurrent epileptic seizures as they age. The syndrome often develops into Lennox-Gastaut syndrome with mixed types of seizures that are difficult to control and is associated with intellectual disability. (For more information on Lennox-Gastaut syndrome, see the Related Disorders section below.). Approximately another third of children with West syndrome will continue to have epileptic spasms at an older age . The last third to quarter of patients will have spasms that resolve with time, usually in patients who have no clear etiology.
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Causes of West Syndrome
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A specific cause for West syndrome can be identified in approximately 70-75% of those affected. Any disorder that can lead to brain damage can be an underlying cause of West syndrome including trauma, brain malformations such as hemimegalencephaly or cortical dysplasia, infections, chromosomal abnormalities such as Down syndrome, neurocutaneous disorders such as tuberous sclerosis complex (TSC), Sturge Weber syndrome, incontinentia pigmenti, different metabolic/genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup urine disorder, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency, Otahara’s syndrome, and an abnormality (mutation) in the ARX gene or CDKL5 gene located on the X chromosome.The most common disorder responsible for West syndrome is tuberous sclerosis complex. (TSC). TSC is an autosomal dominant genetic condition associated with seizures, eye, heart and kidney tumors and skin findings. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.X-linked West syndrome can be caused by a mutation in the CDKL5 gene or the ARX gene in the X chromosome. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly in males. Females that have a non-working 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 only one carries the non-working gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working 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. If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his 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.
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Causes of West Syndrome. A specific cause for West syndrome can be identified in approximately 70-75% of those affected. Any disorder that can lead to brain damage can be an underlying cause of West syndrome including trauma, brain malformations such as hemimegalencephaly or cortical dysplasia, infections, chromosomal abnormalities such as Down syndrome, neurocutaneous disorders such as tuberous sclerosis complex (TSC), Sturge Weber syndrome, incontinentia pigmenti, different metabolic/genetic diseases such as pyridoxine deficiency, non-ketotic hyperglycemia, maple syrup urine disorder, phenylketonuria, mitochondrial encephalopathies and biotinidase deficiency, Otahara’s syndrome, and an abnormality (mutation) in the ARX gene or CDKL5 gene located on the X chromosome.The most common disorder responsible for West syndrome is tuberous sclerosis complex. (TSC). TSC is an autosomal dominant genetic condition associated with seizures, eye, heart and kidney tumors and skin findings. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females.X-linked West syndrome can be caused by a mutation in the CDKL5 gene or the ARX gene in the X chromosome. X-linked genetic disorders are conditions caused by a non-working gene on the X chromosome and manifest mostly in males. Females that have a non-working 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 only one carries the non-working gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a non-working 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. If a male with an X-linked disorder is able to reproduce, he will pass the non-working gene to all of his 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.
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Affects of West Syndrome
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West syndrome is a rare neurological syndrome that can affect males and females. The X-linked form of West syndrome affects males more often than females.West syndrome has been estimated to affect .31 per 1000 live births in the United States. West syndrome accounts for approximately 30 percent of all cases of epilepsy affecting infants.
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Affects of West Syndrome. West syndrome is a rare neurological syndrome that can affect males and females. The X-linked form of West syndrome affects males more often than females.West syndrome has been estimated to affect .31 per 1000 live births in the United States. West syndrome accounts for approximately 30 percent of all cases of epilepsy affecting infants.
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Related disorders of West Syndrome
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Symptoms of the following disorders can be similar to those of West syndrome. Comparisons may be useful for a differential diagnosis:Epilepsy is a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks are frequently preceded by an “aura”, a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. There are many different types of epilepsy and the exact cause is generally unknown. Epileptic spasm is a type of epilepsy.Lennox-Gastaut syndrome (LGS) is a rare type of epilepsy disorder that typically becomes apparent during infancy or early childhood. The disorder is characterized by seizures and, in many cases, abnormal delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor delayes). Individuals with the disorder may experience several different types of seizures. Lennox-Gastaut syndrome may be due to, or occur in association with, a number of different underlying disorders or conditions. (For more information on this disorder, choose “Lennox-Gastaut” as your search term in the Rare Disease Database.)Myoclonic seizures can be seen in numerous types of epilepsies ranging from myoclonic epilepsy of infancy to Dravet syndrome or myoclonic astatic epilepsy and are often times confused with infantile spasms. These types of seizures are quick jerks of the arms and legs, faster than in infantile spasms and sometimes occur singly rather than in epileptic spasms that tend to occur in clusters.As epileptic spasms are very subtle seizures with small brief movements of the trunk or arms, it can be easily misdiagnosed as gastroesophageal reflux, constipation, behavior and other types of non-neurological illness.Myoclonus is a neurological movement disorder in which there are sudden involuntary muscle contractions. There are many different types of myoclonus including some that are hereditary. Other causes include lack of oxygen, viral, malignancies, and lesions of the central nervous system along with drugs and metabolic disorders.
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Related disorders of West Syndrome. Symptoms of the following disorders can be similar to those of West syndrome. Comparisons may be useful for a differential diagnosis:Epilepsy is a group of neurological disorders characterized by abnormal electrical discharges in the brain. It is characterized by loss of consciousness, convulsions, spasms, sensory confusion, and disturbances in the autonomic nervous system. Attacks are frequently preceded by an “aura”, a feeling of unease or sensory discomfort; the aura marks the beginning of the seizure in the brain. There are many different types of epilepsy and the exact cause is generally unknown. Epileptic spasm is a type of epilepsy.Lennox-Gastaut syndrome (LGS) is a rare type of epilepsy disorder that typically becomes apparent during infancy or early childhood. The disorder is characterized by seizures and, in many cases, abnormal delays in the acquisition of skills that require the coordination of mental and muscular activity (psychomotor delayes). Individuals with the disorder may experience several different types of seizures. Lennox-Gastaut syndrome may be due to, or occur in association with, a number of different underlying disorders or conditions. (For more information on this disorder, choose “Lennox-Gastaut” as your search term in the Rare Disease Database.)Myoclonic seizures can be seen in numerous types of epilepsies ranging from myoclonic epilepsy of infancy to Dravet syndrome or myoclonic astatic epilepsy and are often times confused with infantile spasms. These types of seizures are quick jerks of the arms and legs, faster than in infantile spasms and sometimes occur singly rather than in epileptic spasms that tend to occur in clusters.As epileptic spasms are very subtle seizures with small brief movements of the trunk or arms, it can be easily misdiagnosed as gastroesophageal reflux, constipation, behavior and other types of non-neurological illness.Myoclonus is a neurological movement disorder in which there are sudden involuntary muscle contractions. There are many different types of myoclonus including some that are hereditary. Other causes include lack of oxygen, viral, malignancies, and lesions of the central nervous system along with drugs and metabolic disorders.
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Diagnosis of West Syndrome
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Evaluations
The first step is to characterize the patterns of brain activity through measurement with various devices. Among these are:Electroencephalography (EEG):
This is a painless and non-invasive means of recording the patterns of electrical activity of the brain. Electrodes are placed on the scalp and pick up and record the electrical waves during periods of activity and, with luck, during periods of sleep. If a pattern called hypsarrhythmia is noted, especially during sleep, this can help to suggest that a patient has epileptic spasms. However, there are times when a patient may have epileptic spasms and does not have the hypsarrhythmia pattern due to a lag time between clinical symptoms and EEG pattern. In addition, there are several illnesses that can mimic epileptic spasms and a long-term videoEEG may confirm the diagnosis of epileptic spasms. Therefore, an overnight, long term video EEG monitoring is preferable compared to a routine 20-minute EEG study in cases of epileptic spasms.Brain Scans, such as:
Computed Tomography (CT). Harnessing X-rays to a computer generates pictures of cross-sections of the brain from which the detail of development may be determined. CT is also very good at showing areas of calcification that in some cases, may be essential for the diagnosis. However, this does not provide as detailed a picture as a MRI.Magnetic Resonance Imaging (MRI). This radiological technique produces detailed images of cross-sections or slices of the brain by using the magnetic properties of particular atoms found in the brain. The images are more detailed than a CT and can provide information concerning any malformations of the brain structures or other types of lesions commonly seen in epileptic spasms.Infection as a cause of epileptic spasms may be determined by blood tests, urine tests and lumbar puncture.A Wood’s lamp is used to examine skin for lesions with lack of pigment in order to determine if tuberous sclerosis is a possible diagnosis.Molecular genetic testing is available for mutations in the ARX and CDKL5 genes associated with X-linked West syndrome. It is also available for the genes associated with tuberous sclerosis complex. Some genetic disorders will require cerebrospinal fluid (CSF) for genetic testing. Testing for nonketotic hyperglycemia may require a CSF sample to test for glycine and testing for mitochondrial diseases may require CSF to test for lactate. A mutation in the STXBP1 gene has recently been noted in patients with Otahara’s syndrome as well. There are several genetic panels available that can test children of a certain age for a variety of genetic conditions that are seen in epilepsies such as epileptic spasms.
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Diagnosis of West Syndrome. Evaluations
The first step is to characterize the patterns of brain activity through measurement with various devices. Among these are:Electroencephalography (EEG):
This is a painless and non-invasive means of recording the patterns of electrical activity of the brain. Electrodes are placed on the scalp and pick up and record the electrical waves during periods of activity and, with luck, during periods of sleep. If a pattern called hypsarrhythmia is noted, especially during sleep, this can help to suggest that a patient has epileptic spasms. However, there are times when a patient may have epileptic spasms and does not have the hypsarrhythmia pattern due to a lag time between clinical symptoms and EEG pattern. In addition, there are several illnesses that can mimic epileptic spasms and a long-term videoEEG may confirm the diagnosis of epileptic spasms. Therefore, an overnight, long term video EEG monitoring is preferable compared to a routine 20-minute EEG study in cases of epileptic spasms.Brain Scans, such as:
Computed Tomography (CT). Harnessing X-rays to a computer generates pictures of cross-sections of the brain from which the detail of development may be determined. CT is also very good at showing areas of calcification that in some cases, may be essential for the diagnosis. However, this does not provide as detailed a picture as a MRI.Magnetic Resonance Imaging (MRI). This radiological technique produces detailed images of cross-sections or slices of the brain by using the magnetic properties of particular atoms found in the brain. The images are more detailed than a CT and can provide information concerning any malformations of the brain structures or other types of lesions commonly seen in epileptic spasms.Infection as a cause of epileptic spasms may be determined by blood tests, urine tests and lumbar puncture.A Wood’s lamp is used to examine skin for lesions with lack of pigment in order to determine if tuberous sclerosis is a possible diagnosis.Molecular genetic testing is available for mutations in the ARX and CDKL5 genes associated with X-linked West syndrome. It is also available for the genes associated with tuberous sclerosis complex. Some genetic disorders will require cerebrospinal fluid (CSF) for genetic testing. Testing for nonketotic hyperglycemia may require a CSF sample to test for glycine and testing for mitochondrial diseases may require CSF to test for lactate. A mutation in the STXBP1 gene has recently been noted in patients with Otahara’s syndrome as well. There are several genetic panels available that can test children of a certain age for a variety of genetic conditions that are seen in epilepsies such as epileptic spasms.
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Therapies of West Syndrome
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Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.In some children, it is possible that treatment with anticonvulsant drugs may help reduce or control various types of seizure activity associated with West syndrome. The most common medications used to treat epileptic spasms include adrenocorticotropic hormone (ACTH), prednisone, vigabatrin and pyridoxine. The benefits of the medication need to be weighed with the risks of side effects of each treatment. For example, ACTH, prednisone and other steroids are known to cause issues with immunosuppression, hypertension, glucose, gastric issues, agitation and irritability. Vigabatrin may cause an irreversible visual field defect, irritability, and transient hyperintensity of deep structures in the MRI. There is no standard protocol for using ACTH or other steroid treatment. It is unknown whether high dose ACTH or low dose ACTH is effective or whether the use of prednisone is more effective than ACTH. In a recent multicenter study looking at steroid treatment compared to vigabatrin, it was felt that steroids may have better seizure control compared to vigabatrin at 2 weeks of treatment, but that the effectiveness was the same after a year. In addition, vigabatrin was more effective in patients with tuberous sclerosis or cortical dysplasia compared to steroids. More recently a multicenter European/Australian/New Zealand consortium (ISCC) found that hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The investigations in the US are ongoing for combination hormonal and vigabatrin therapy. It is felt that a shorter time between diagnosis and treatment will have a less deleterious effect on development compared to a longer lead-time to treatment. If these treatments are not successful, other medications such as benzodiazepines (for example, clobazam), valproic acid, topiramate, rufinamide and zonisamide may be used. Ketogenic diet has also been successful at times in the treatment of epileptic spasms. Finally, in cases where there is a malformation or tuberous sclerosis complex, epilepsy surgery may be helpful to control spasms.
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Therapies of West Syndrome. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, neurologists, surgeons, and/or other health care professionals may need to systematically and comprehensively plan an affected child’s treatment.In some children, it is possible that treatment with anticonvulsant drugs may help reduce or control various types of seizure activity associated with West syndrome. The most common medications used to treat epileptic spasms include adrenocorticotropic hormone (ACTH), prednisone, vigabatrin and pyridoxine. The benefits of the medication need to be weighed with the risks of side effects of each treatment. For example, ACTH, prednisone and other steroids are known to cause issues with immunosuppression, hypertension, glucose, gastric issues, agitation and irritability. Vigabatrin may cause an irreversible visual field defect, irritability, and transient hyperintensity of deep structures in the MRI. There is no standard protocol for using ACTH or other steroid treatment. It is unknown whether high dose ACTH or low dose ACTH is effective or whether the use of prednisone is more effective than ACTH. In a recent multicenter study looking at steroid treatment compared to vigabatrin, it was felt that steroids may have better seizure control compared to vigabatrin at 2 weeks of treatment, but that the effectiveness was the same after a year. In addition, vigabatrin was more effective in patients with tuberous sclerosis or cortical dysplasia compared to steroids. More recently a multicenter European/Australian/New Zealand consortium (ISCC) found that hormonal therapy with vigabatrin is significantly more effective at stopping infantile spasms than hormonal therapy alone. The investigations in the US are ongoing for combination hormonal and vigabatrin therapy. It is felt that a shorter time between diagnosis and treatment will have a less deleterious effect on development compared to a longer lead-time to treatment. If these treatments are not successful, other medications such as benzodiazepines (for example, clobazam), valproic acid, topiramate, rufinamide and zonisamide may be used. Ketogenic diet has also been successful at times in the treatment of epileptic spasms. Finally, in cases where there is a malformation or tuberous sclerosis complex, epilepsy surgery may be helpful to control spasms.
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Overview of WHIM Syndrome
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SummaryWHIM syndrome is a rare primary immunodeficiency disorder, which are disorders in which the body’s immune system does not function properly. WHIM is an acronym for some of the characteristic symptoms of the disorder – (w)arts, (h)ypogammaglobulinemia, (i)nfections, and (m)yelokathexis. Individuals with WHIM syndrome are more susceptible to potentially life-threatening bacterial infections. To a lesser extent, they are also predisposed to viral infections. Affected individuals are particularly susceptible to human papillomavirus (HPV), which can cause skin and genital warts and potentially lead to cancer. Affected individuals have extremely low levels of certain white blood cells (neutrophils) leading to a condition called neutropenia. In most patients, WHIM syndrome is caused by changes (mutations) in the CXCR4 gene. This mutation is inherited in an autosomal dominant pattern.IntroductionWHIM syndrome is a primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g. saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells.
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Overview of WHIM Syndrome. SummaryWHIM syndrome is a rare primary immunodeficiency disorder, which are disorders in which the body’s immune system does not function properly. WHIM is an acronym for some of the characteristic symptoms of the disorder – (w)arts, (h)ypogammaglobulinemia, (i)nfections, and (m)yelokathexis. Individuals with WHIM syndrome are more susceptible to potentially life-threatening bacterial infections. To a lesser extent, they are also predisposed to viral infections. Affected individuals are particularly susceptible to human papillomavirus (HPV), which can cause skin and genital warts and potentially lead to cancer. Affected individuals have extremely low levels of certain white blood cells (neutrophils) leading to a condition called neutropenia. In most patients, WHIM syndrome is caused by changes (mutations) in the CXCR4 gene. This mutation is inherited in an autosomal dominant pattern.IntroductionWHIM syndrome is a primary immunodeficiency disorder, one of a group of disorders characterized by irregularities in the cell development and/or cell maturation process of the immune system. The immune system is divided into several components, the combined actions of which are responsible for defending against infectious agents. The T cell system (cell-mediated immune response) contributes to fighting several viruses, some bacteria and yeast and fungi. The B cell system (humoral immune response) fights infection caused by other viruses and bacteria. It does so by secreting immune factors called antibodies (also known as immunoglobulins) into the fluid portion of the blood (serum) and body secretions (e.g. saliva). There are five classes of immunoglobulins (Ig) known as IgA, IgD, IgE, IgG, and IgM. Antibodies can directly kill microorganisms or coat them so they are more easily destroyed by white blood cells.
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Symptoms of WHIM Syndrome
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The symptoms of WHIM syndrome can vary greatly from one individual to another. Some individuals may have mild expression of the disorder and others may develop potentially life-threatening complications. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disease outcome prevent physicians from developing a perfectly accurate picture of associated symptoms and prognosis.Generally, symptoms first appear in early childhood when most children with WHIM syndrome experience repeated bacterial infections that can be mild or severe, but usually respond promptly to antibiotic therapy. The number and frequency of infections can vary greatly from one individual to another. Common infections in children with WHIM syndrome include recurrent middle ear infections (otitis media), infection of the skin and underlying tissue (cellulitis, impetigo, folliculitis, and abscess), bacterial pneumonia, sinusitis, painful infections of the joints (septic arthritis), dental cavities, and infection of the gums (periodontitis). Bone infection (osteomyelitis), urinary tract infections, and infection of the membranes covering the brain (meningitis) have also been reported. Chronic infections can potentially cause additional symptoms. For example, some individuals who experience repeated ear infections may experience hearing loss. Dental infections can lead to tooth loss. Some individuals who experience repeated episodes of pneumonia may eventually develop destruction and widening of the airway tubes that carry air in and out of the lungs (bronchiectasis). Bronchiectasis can further lead to repeated lung infections and potentially serious complications including respiratory failure, lung collapse (atelectasis), and heart failure. Some affected individuals have developed colonization of their respiratory tract with bacterial organisms such as Pseudomonas and Stenotrophomonas common in another genetic disorder called cystic fibrosis.Upon exposure, affected individuals may develop warts due to infection with human papillomavirus (HPV), a virus that only infects humans and has more than 150 related types. Warts usually develop in the teens, but can be seen in early childhood. Warts may be widespread affecting the hands, feet, face, and trunk and are often recurrent despite treatment (recalcitrant). Mucosal, oral, and genital warts may also develop, and these warts are associated with an increased risk of progressing into a form of cancer known as carcinoma. HPV infection has been linked to cervical carcinoma in WHIM syndrome. Two siblings with WHIM syndrome developed carcinoma of the oral cavity. Myelokathexis is a medical term for characteristic bone marrow pathology findings which include having too many white blood cells present in the bone marrow (hypercellularity). Bone marrow is the spongy substance found in the center of the long bones of the body. The bone marrow produces specialized cells that grow and develop into red blood cells, white blood cells and platelets. These cells are released into the bloodstream to perform their normal functions within the body. However, although neutrophil production occurs normally in individuals with WHIM syndrome, mature neutrophils are retained and eventually die within the bone marrow without being released into the bloodstream. Consequently, affected individuals have low levels of circulating neutrophils (neutropenia) in the blood; however, this can be overcome during periods of severe infection or stress. Neutrophils play a role in the helping the body fight off infection, especially bacterial and fungal infections. In addition to neutropenia, most individuals with WHIM syndrome also have low levels of another type of white blood cell known as a B-lymphocyte. B-lymphocytes make antibodies (immunoglobulins) in response to bacterial or viral infection. Consequently, affected individuals have low levels of certain antibodies, a condition known as hypogammaglobulinemia. The lack of sufficient B-lymphocyte antibodies leaves individuals susceptible to infection with specific types of bacteria or, to a lesser extent, certain viruses. Some affected individuals may also have low levels of other white blood cells such as T cells or natural killer cells. Some individuals have low levels of all white blood cells (panleukopenia). Although the white blood cell counts of affected individuals can be profoundly altered, it appears that the spectrum of infections that occurs in individuals with WHIM syndrome is limited. Additional findings have been reported in specific cases. Two individuals with WHIM syndrome have developed Epstein Barr associated B cell lymphoma. Three affected individuals had a severe congenital heart malformation known as tetralogy of Fallot.
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Symptoms of WHIM Syndrome. The symptoms of WHIM syndrome can vary greatly from one individual to another. Some individuals may have mild expression of the disorder and others may develop potentially life-threatening complications. Several factors including the small number of identified cases, the lack of large clinical studies, and the possibility of other genes influencing the disease outcome prevent physicians from developing a perfectly accurate picture of associated symptoms and prognosis.Generally, symptoms first appear in early childhood when most children with WHIM syndrome experience repeated bacterial infections that can be mild or severe, but usually respond promptly to antibiotic therapy. The number and frequency of infections can vary greatly from one individual to another. Common infections in children with WHIM syndrome include recurrent middle ear infections (otitis media), infection of the skin and underlying tissue (cellulitis, impetigo, folliculitis, and abscess), bacterial pneumonia, sinusitis, painful infections of the joints (septic arthritis), dental cavities, and infection of the gums (periodontitis). Bone infection (osteomyelitis), urinary tract infections, and infection of the membranes covering the brain (meningitis) have also been reported. Chronic infections can potentially cause additional symptoms. For example, some individuals who experience repeated ear infections may experience hearing loss. Dental infections can lead to tooth loss. Some individuals who experience repeated episodes of pneumonia may eventually develop destruction and widening of the airway tubes that carry air in and out of the lungs (bronchiectasis). Bronchiectasis can further lead to repeated lung infections and potentially serious complications including respiratory failure, lung collapse (atelectasis), and heart failure. Some affected individuals have developed colonization of their respiratory tract with bacterial organisms such as Pseudomonas and Stenotrophomonas common in another genetic disorder called cystic fibrosis.Upon exposure, affected individuals may develop warts due to infection with human papillomavirus (HPV), a virus that only infects humans and has more than 150 related types. Warts usually develop in the teens, but can be seen in early childhood. Warts may be widespread affecting the hands, feet, face, and trunk and are often recurrent despite treatment (recalcitrant). Mucosal, oral, and genital warts may also develop, and these warts are associated with an increased risk of progressing into a form of cancer known as carcinoma. HPV infection has been linked to cervical carcinoma in WHIM syndrome. Two siblings with WHIM syndrome developed carcinoma of the oral cavity. Myelokathexis is a medical term for characteristic bone marrow pathology findings which include having too many white blood cells present in the bone marrow (hypercellularity). Bone marrow is the spongy substance found in the center of the long bones of the body. The bone marrow produces specialized cells that grow and develop into red blood cells, white blood cells and platelets. These cells are released into the bloodstream to perform their normal functions within the body. However, although neutrophil production occurs normally in individuals with WHIM syndrome, mature neutrophils are retained and eventually die within the bone marrow without being released into the bloodstream. Consequently, affected individuals have low levels of circulating neutrophils (neutropenia) in the blood; however, this can be overcome during periods of severe infection or stress. Neutrophils play a role in the helping the body fight off infection, especially bacterial and fungal infections. In addition to neutropenia, most individuals with WHIM syndrome also have low levels of another type of white blood cell known as a B-lymphocyte. B-lymphocytes make antibodies (immunoglobulins) in response to bacterial or viral infection. Consequently, affected individuals have low levels of certain antibodies, a condition known as hypogammaglobulinemia. The lack of sufficient B-lymphocyte antibodies leaves individuals susceptible to infection with specific types of bacteria or, to a lesser extent, certain viruses. Some affected individuals may also have low levels of other white blood cells such as T cells or natural killer cells. Some individuals have low levels of all white blood cells (panleukopenia). Although the white blood cell counts of affected individuals can be profoundly altered, it appears that the spectrum of infections that occurs in individuals with WHIM syndrome is limited. Additional findings have been reported in specific cases. Two individuals with WHIM syndrome have developed Epstein Barr associated B cell lymphoma. Three affected individuals had a severe congenital heart malformation known as tetralogy of Fallot.
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Causes of WHIM Syndrome
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WHIM syndrome is caused by several different mutations in the chemokine receptor (CXCR4) 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 or have increased function. A single protein can affect many organ systems of the body. In the case of the known mutations that cause WHIM syndrome, the mutations make the protein hyperfunctional and are thus called gain-of-function mutations. The CXCR4 gene creates (encodes) a chemokine receptor known as CXCR4. Chemokines are a special class of protein that are involved in cell trafficking. Cell trafficking is a normal process in which certain cells receive instructions telling them where in the body they should travel (migrate) to and when to stop. Mutations in the CXCR4 gene lead to increased activity of the CXCR4 protein product. It is not fully understood how increased activity of this chemokine receptor affects B cell number and function or leads to HPV susceptibility. Some studies have suggested that increased CXCR4 activity acts on mature neutrophils preventing their release from the bone marrow. More research is necessary to determine the complex, underlying mechanisms that cause WHIM syndrome. Some individuals with the characteristic symptoms of WHIM syndrome do not have a detectable mutation in the CXCR4 gene suggesting that the disorder may have other genetic causes.WHIM syndrome is inherited in an autosomal dominant pattern. 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 (sproradic or de novo gene change) in the affected individual. In the latter case, 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 found to be affected. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females. The disorder is usually not inherited from or “carried” by a healthy parent.
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Causes of WHIM Syndrome. WHIM syndrome is caused by several different mutations in the chemokine receptor (CXCR4) 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 or have increased function. A single protein can affect many organ systems of the body. In the case of the known mutations that cause WHIM syndrome, the mutations make the protein hyperfunctional and are thus called gain-of-function mutations. The CXCR4 gene creates (encodes) a chemokine receptor known as CXCR4. Chemokines are a special class of protein that are involved in cell trafficking. Cell trafficking is a normal process in which certain cells receive instructions telling them where in the body they should travel (migrate) to and when to stop. Mutations in the CXCR4 gene lead to increased activity of the CXCR4 protein product. It is not fully understood how increased activity of this chemokine receptor affects B cell number and function or leads to HPV susceptibility. Some studies have suggested that increased CXCR4 activity acts on mature neutrophils preventing their release from the bone marrow. More research is necessary to determine the complex, underlying mechanisms that cause WHIM syndrome. Some individuals with the characteristic symptoms of WHIM syndrome do not have a detectable mutation in the CXCR4 gene suggesting that the disorder may have other genetic causes.WHIM syndrome is inherited in an autosomal dominant pattern. 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 (sproradic or de novo gene change) in the affected individual. In the latter case, 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 found to be affected. The risk of passing the abnormal gene from affected parent to offspring is 50 percent for each pregnancy. The risk is the same for males and females. The disorder is usually not inherited from or “carried” by a healthy parent.
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Affects of WHIM Syndrome
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WHIM syndrome is an extremely rare disorder and its exact prevalence or incidence in the general population is unknown although it has been estimated at about 0.2 / million live births. Approximately 100 cases have been reported in the medical literature. Onset is usually in infancy or early childhood. Males and females are affected in equal numbers.
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Affects of WHIM Syndrome. WHIM syndrome is an extremely rare disorder and its exact prevalence or incidence in the general population is unknown although it has been estimated at about 0.2 / million live births. Approximately 100 cases have been reported in the medical literature. Onset is usually in infancy or early childhood. Males and females are affected in equal numbers.
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Related disorders of WHIM Syndrome
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Symptoms of the following disorders can be similar to or confused with those of WHIM syndrome. Comparisons may be useful for a differential diagnosis. There are many different causes of neutropenia. Neutropenia may result from viral infection, due to the use of certain drugs, and/or following exposure to certain poisons. In addition, in some cases, the body may produce antibodies against neutrophils (autoimmune neutropenia) causing an abnormal decrease in these white blood cells. Neutropenia may also occur as a secondary finding due to another primary disorder (e.g. leukemia). WHIM syndrome is a type of severe congenital neutropenia; however, there are other genetic disorders that are characterized by neutropenia including severe chronic neutropenia, Kostmann syndrome, Barth syndrome, cyclic neutropenia, X-linked congenital neutropenia, and Shwachman-Diamond syndrome. WHIM syndrome can be distinguished from these disorders by examination of the bone marrow which shows myelokathexis and by genetic testing. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)The primary immunodeficiency disorders are a group of disorders characterized by defects in the immune system that result in recurrent bacterial and/or viral infections. Approximately 250 forms of primary immunodeficiency disorders have been identified. Some of these disorders may have signs and symptoms that are similar to those found in WHIM syndrome and may cause severe problems with warts. In particular, mutations in the STK4 (MST1) and GATA2 genes can cause severe problems with warts and neutropenia. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Related disorders of WHIM Syndrome. Symptoms of the following disorders can be similar to or confused with those of WHIM syndrome. Comparisons may be useful for a differential diagnosis. There are many different causes of neutropenia. Neutropenia may result from viral infection, due to the use of certain drugs, and/or following exposure to certain poisons. In addition, in some cases, the body may produce antibodies against neutrophils (autoimmune neutropenia) causing an abnormal decrease in these white blood cells. Neutropenia may also occur as a secondary finding due to another primary disorder (e.g. leukemia). WHIM syndrome is a type of severe congenital neutropenia; however, there are other genetic disorders that are characterized by neutropenia including severe chronic neutropenia, Kostmann syndrome, Barth syndrome, cyclic neutropenia, X-linked congenital neutropenia, and Shwachman-Diamond syndrome. WHIM syndrome can be distinguished from these disorders by examination of the bone marrow which shows myelokathexis and by genetic testing. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)The primary immunodeficiency disorders are a group of disorders characterized by defects in the immune system that result in recurrent bacterial and/or viral infections. Approximately 250 forms of primary immunodeficiency disorders have been identified. Some of these disorders may have signs and symptoms that are similar to those found in WHIM syndrome and may cause severe problems with warts. In particular, mutations in the STK4 (MST1) and GATA2 genes can cause severe problems with warts and neutropenia. (For more information on these disorders, choose the specific disorder name as your search term in the Rare Disease Database.)
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Diagnosis of WHIM Syndrome
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A diagnosis of WHIM syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including genetic tests. Individuals with a history of recurrent bacterial infections, neutropenia, and recalcitrant warts should be tested for WHIM syndrome. Clinical Testing and Workup
A complete blood count with differential (CBC + Diff) will show low levels of neutrophils (neutropenia) in uninfected patients, a variable degree of lymphopenia, and normal to low hemoglobulin and platelet levels. Initial workups can also reveal hypogammaglobulinemia (low IgG) or poor response to vaccinations. If WHIM syndrome is suspected based on initial tests, the surgical removal and microscopic examination of bone marrow tissue (bone marrow biopsy) may be performed. A bone marrow biopsy can reveal myelokathexis, which along with characteristic findings, is strongly suggestive of WHIM syndrome. In most patients, molecular genetic testing can confirm a diagnosis of WHIM syndrome. Molecular genetic testing can detect mutations in the CXCR4 gene known to cause the disorder and is available at the National Institutes of Health at no charge if clinically indicated and informed consent is given.
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Diagnosis of WHIM Syndrome. A diagnosis of WHIM syndrome is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests including genetic tests. Individuals with a history of recurrent bacterial infections, neutropenia, and recalcitrant warts should be tested for WHIM syndrome. Clinical Testing and Workup
A complete blood count with differential (CBC + Diff) will show low levels of neutrophils (neutropenia) in uninfected patients, a variable degree of lymphopenia, and normal to low hemoglobulin and platelet levels. Initial workups can also reveal hypogammaglobulinemia (low IgG) or poor response to vaccinations. If WHIM syndrome is suspected based on initial tests, the surgical removal and microscopic examination of bone marrow tissue (bone marrow biopsy) may be performed. A bone marrow biopsy can reveal myelokathexis, which along with characteristic findings, is strongly suggestive of WHIM syndrome. In most patients, molecular genetic testing can confirm a diagnosis of WHIM syndrome. Molecular genetic testing can detect mutations in the CXCR4 gene known to cause the disorder and is available at the National Institutes of Health at no charge if clinically indicated and informed consent is given.
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Therapies of WHIM Syndrome
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TreatmentThe treatment of WHIM 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, immunologists, hematologists, dermatologists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Prompt diagnosis and early aggressive treatment of infections is important to reduce long term damage. Treatment may include injection of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF), which can help to normalize neutrophil counts. These drugs stimulate the production and maturation of neutrophils. Another therapy used to treat individuals with WHIM syndrome is monthly infusions with purified antibodies (immunoglobulins) obtained from human plasma, the fluid portion of the blood. This therapy is known as intravenous immunoglobulin or IVIG. IVIG therapy can treat hypogammaglobulinemia and can help reduce the frequency of the recurrent infections characteristic of WHIM syndrome. Immunoglobulin therapy can also be given subcutaneously on a weekly basis. The preventative (prophylactic) use of antibiotics has not been studied in WHIM syndrome, but has proven effective in other primary immunodeficiency disorders. HPV-associated warts frequently recur after surgery or other conventional therapy. Affected individuals should be regularly monitored to promptly detect and surgically remove within the early stages any HPV lesions that appear pre-malignant or malignant.Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.
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Therapies of WHIM Syndrome. TreatmentThe treatment of WHIM 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, immunologists, hematologists, dermatologists, and other healthcare professionals may need to systematically and comprehensively plan an affected child’s treatment. Prompt diagnosis and early aggressive treatment of infections is important to reduce long term damage. Treatment may include injection of granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF), which can help to normalize neutrophil counts. These drugs stimulate the production and maturation of neutrophils. Another therapy used to treat individuals with WHIM syndrome is monthly infusions with purified antibodies (immunoglobulins) obtained from human plasma, the fluid portion of the blood. This therapy is known as intravenous immunoglobulin or IVIG. IVIG therapy can treat hypogammaglobulinemia and can help reduce the frequency of the recurrent infections characteristic of WHIM syndrome. Immunoglobulin therapy can also be given subcutaneously on a weekly basis. The preventative (prophylactic) use of antibiotics has not been studied in WHIM syndrome, but has proven effective in other primary immunodeficiency disorders. HPV-associated warts frequently recur after surgery or other conventional therapy. Affected individuals should be regularly monitored to promptly detect and surgically remove within the early stages any HPV lesions that appear pre-malignant or malignant.Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well.
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Overview of Whipple Disease
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Whipple disease is a rare disease resulting from bacterial infection that leads to inadequate absorption of nutrients (malabsorption) from the intestine. It is believed to result from infection with bacteria known as Tropheryma whippelii. The infection usually involves the small intestine, but over time, the disease may affect various parts of the body, including the heart, lungs, brain, and eyes.
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Overview of Whipple Disease. Whipple disease is a rare disease resulting from bacterial infection that leads to inadequate absorption of nutrients (malabsorption) from the intestine. It is believed to result from infection with bacteria known as Tropheryma whippelii. The infection usually involves the small intestine, but over time, the disease may affect various parts of the body, including the heart, lungs, brain, and eyes.
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Symptoms of Whipple Disease
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The major symptoms of Whipple disease include abdominal pain after eating, joint pain, bouts of diarrhea, cough, chest pain, general weakness, and night sweats. Typically there is fat present in the stool (steatorrhea). Weight loss may occur because of a profound lack of appetite (anorexia). Anemia may result due to insufficient levels of iron, and pain may occur in several widely scattered joints (polyarthritis).Other symptoms of Whipple disease may include: abnormally enlarged lymph nodes that are firm but usually not tender, an abnormally enlarged spleen (splenomegaly), increased color (pigmentation) of the skin, a decrease in blood pressure (hypotension), and abnormally high fevers that come and go. Some people with this disorder may experience a decrease in intellectual abilities, and an impairment of memory, judgment, and/or abstract thought. Occasionally, the loss of intellectual skills progresses to dementia. Eye movements may be impaired and uncontrolled muscular movements (myoclonus) may occur when Whipple disease has affected the brain or central nervous system. (For more information on this disorder, choose “Myoclonus” as your search term in the Rare Disease Database.)The central nervous system is affected in the later stages of untreated Whipple disease. Symptoms of neurological involvement may include hearing loss, persistent ringing in the ears (tinnitus), and impairment of vision. (For more information on this disorder, choose “Tinnitus” as your search term in the Rare Disease Database.) In rare cases of this disorder, the heart may be affected resulting in congestive heart failure and/or inflammation of the membranes that surround the heart (pericarditis).If Whipple disease remains untreated and malabsorption from the small intestine becomes worse, the affected person may have low levels of circulating calcium and magnesium in the blood (hypokalemia and hypomagnesemia) resulting in muscle cramps, convulsions, and twitching (tetany). Damage to the nerves, especially those of the arms and legs (peripheral neuropathy) may also occur. (For more information on these disorders, choose “Neuropathy, Peripheral” as your search term in the Rare Disease Database.)
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Symptoms of Whipple Disease. The major symptoms of Whipple disease include abdominal pain after eating, joint pain, bouts of diarrhea, cough, chest pain, general weakness, and night sweats. Typically there is fat present in the stool (steatorrhea). Weight loss may occur because of a profound lack of appetite (anorexia). Anemia may result due to insufficient levels of iron, and pain may occur in several widely scattered joints (polyarthritis).Other symptoms of Whipple disease may include: abnormally enlarged lymph nodes that are firm but usually not tender, an abnormally enlarged spleen (splenomegaly), increased color (pigmentation) of the skin, a decrease in blood pressure (hypotension), and abnormally high fevers that come and go. Some people with this disorder may experience a decrease in intellectual abilities, and an impairment of memory, judgment, and/or abstract thought. Occasionally, the loss of intellectual skills progresses to dementia. Eye movements may be impaired and uncontrolled muscular movements (myoclonus) may occur when Whipple disease has affected the brain or central nervous system. (For more information on this disorder, choose “Myoclonus” as your search term in the Rare Disease Database.)The central nervous system is affected in the later stages of untreated Whipple disease. Symptoms of neurological involvement may include hearing loss, persistent ringing in the ears (tinnitus), and impairment of vision. (For more information on this disorder, choose “Tinnitus” as your search term in the Rare Disease Database.) In rare cases of this disorder, the heart may be affected resulting in congestive heart failure and/or inflammation of the membranes that surround the heart (pericarditis).If Whipple disease remains untreated and malabsorption from the small intestine becomes worse, the affected person may have low levels of circulating calcium and magnesium in the blood (hypokalemia and hypomagnesemia) resulting in muscle cramps, convulsions, and twitching (tetany). Damage to the nerves, especially those of the arms and legs (peripheral neuropathy) may also occur. (For more information on these disorders, choose “Neuropathy, Peripheral” as your search term in the Rare Disease Database.)
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Causes of Whipple Disease
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Whipple disease is caused by a rod-shaped bacterium called Tropheryma whippelii. This bacterium was first identified in 1991/92. Its natural habitats are unknown, but it appears likely that infection occurs by way of an environmental source and that the bacteria are introduced into the body through the mouth (peroral).
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Causes of Whipple Disease. Whipple disease is caused by a rod-shaped bacterium called Tropheryma whippelii. This bacterium was first identified in 1991/92. Its natural habitats are unknown, but it appears likely that infection occurs by way of an environmental source and that the bacteria are introduced into the body through the mouth (peroral).
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Affects of Whipple Disease
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Whipple disease affects more males than females in a ratio of approximately 4 to 1. The symptoms of this disorder typically begin between the ages of thirty and sixty years. The age range of those affected is thought to be between 30 and 80, with the median age at time of diagnosis being 56 years. Most of the cases of Whipple disease have been diagnosed among Europeans and Americans of European parentage. In Germany, the disease incidence has been estimated at 0.4 per million population per year. A few cases have been reported among American Indians and Americans of African descent. In 2004, for the first time, a case of Whipple disease was reported in Japan.
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Affects of Whipple Disease. Whipple disease affects more males than females in a ratio of approximately 4 to 1. The symptoms of this disorder typically begin between the ages of thirty and sixty years. The age range of those affected is thought to be between 30 and 80, with the median age at time of diagnosis being 56 years. Most of the cases of Whipple disease have been diagnosed among Europeans and Americans of European parentage. In Germany, the disease incidence has been estimated at 0.4 per million population per year. A few cases have been reported among American Indians and Americans of African descent. In 2004, for the first time, a case of Whipple disease was reported in Japan.
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Related disorders of Whipple Disease
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Symptoms of the following disorders can be similar to those of Whipple disease. Comparisons may be useful for a differential diagnosis:Crohn's disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. Symptoms may include vomiting, fever, night sweats, loss of appetite, general weakness, and waves of abdominal pain and discomfort. Diarrhea and bleeding from the rectum are common in people who have Crohn's disease. Weight loss is also common. The symptoms of this disorder can be difficult to manage and diagnosis is often delayed. (For information on this disorder, choose “Crohn's Disease” as your search term in the Rare Disease Database.)Ulcerative colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and urgency (tenesmus). Weight loss and a decrease in appetite are also associated with ulcerative colitis. (For more information on this disorder, choose “Ulcerative Colitis” as your search term in the Rare Disease Database.)Primary sclerosing cholangitis is a rare collagen disorder involving inflammation and blockage of the bile duct, liver ducts, and gallbladder. Symptoms of this disorder include abdominal pain, loss of appetite, nausea, vomiting, and/or weight loss. Later symptoms may include a yellow discoloration to the skin (jaundice), fever, chills, and/or itching of the skin. Bacterial infections may be associated with bile duct blockages of primary sclerosing cholangitis. (For more information on this disorder, choose “Primary Sclerosing Cholangitis,” as your search term in the Rare Disease Database.)Chronic erosive gastritis is an inflammatory digestive disorder characterized by multiple lesions in the mucus lining of the stomach. Symptoms of this disorder may include burning or a heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of chronic erosive gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose “Chronic Erosive Gastritis” as your search term in the Rare Disease Database.)Irritable bowel syndrome, also known as spastic colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with irritable bowel syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose “Irritable Bowel Syndrome” as your search term in the Rare Disease Database.)Intestinal pseudoobstruction is a gastrointestinal disorder characterized by a lack of motility of the intestine. This condition resembles a true obstruction although there is no evidence of any physical obstruction. Symptoms may include constipation, colicky pain, vomiting, and weight loss. Intestinal pseudoobstruction may also affect speech, muscle activity, and the nervous system. (For more information on this disorder, choose “Intestinal Pseudoobstruction, Intestinal” as your search term in the Rare Disease Database.)Giant hypertrophic gastritis is a chronic disorder characterized by the presence of large, coiled ridges or folds, in the inner wall of the stomach. Symptoms include abdominal pain or discomfort and tenderness in the upper middle region of the abdomen. Other symptoms may include a profound loss of appetite, nausea, vomiting, and diarrhea. (For more information on this disorder, choose “Giant Hypertrophic Gastritis” as your search term in the Rare Disease Database.)Acquired immune deficiency syndrome (AIDS) is an immunosuppressive disorder caused by infection with the human immunodeficiency virus (HIV). The immune deficiency is a result of a viral infection and the destruction of specific T cells. Initially HIV infection is characterized by a period without symptoms. This may be followed by the development of swollen lymph nodes (lymphadenopathy). Eventually most people with acquired immune deficiency syndrome experience a progression of symptoms that occur as a result of a compromised immune system. When a person with AIDS has an intestinal infection with Mycobacterium avium intracellulare, the symptoms may be confused with those of Whipple disease. (For more information on this disorder, choose “AIDS” as your search term in the Rare Disease Database.)
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Related disorders of Whipple Disease. Symptoms of the following disorders can be similar to those of Whipple disease. Comparisons may be useful for a differential diagnosis:Crohn's disease is an inflammatory bowel disease characterized by severe, chronic inflammation of the intestinal wall or any portion of the gastrointestinal tract. Symptoms may include vomiting, fever, night sweats, loss of appetite, general weakness, and waves of abdominal pain and discomfort. Diarrhea and bleeding from the rectum are common in people who have Crohn's disease. Weight loss is also common. The symptoms of this disorder can be difficult to manage and diagnosis is often delayed. (For information on this disorder, choose “Crohn's Disease” as your search term in the Rare Disease Database.)Ulcerative colitis is an acute inflammatory bowel disease characterized by diarrhea and blood in the stools because of multiple, irregular ulcerations of the bowel. The initial symptoms of this disorder may include a general feeling of weakness (malaise) and fatigue. There may be abdominal discomfort, along with a change in the frequency and consistency of stools. Other symptoms may include abdominal pain, cramping, and urgency (tenesmus). Weight loss and a decrease in appetite are also associated with ulcerative colitis. (For more information on this disorder, choose “Ulcerative Colitis” as your search term in the Rare Disease Database.)Primary sclerosing cholangitis is a rare collagen disorder involving inflammation and blockage of the bile duct, liver ducts, and gallbladder. Symptoms of this disorder include abdominal pain, loss of appetite, nausea, vomiting, and/or weight loss. Later symptoms may include a yellow discoloration to the skin (jaundice), fever, chills, and/or itching of the skin. Bacterial infections may be associated with bile duct blockages of primary sclerosing cholangitis. (For more information on this disorder, choose “Primary Sclerosing Cholangitis,” as your search term in the Rare Disease Database.)Chronic erosive gastritis is an inflammatory digestive disorder characterized by multiple lesions in the mucus lining of the stomach. Symptoms of this disorder may include burning or a heavy feeling in the stomach, mild nausea, vomiting, loss of appetite and general weakness. In severe cases of chronic erosive gastritis there may be bleeding from the stomach that can result in anemia. (For more information on this disorder, choose “Chronic Erosive Gastritis” as your search term in the Rare Disease Database.)Irritable bowel syndrome, also known as spastic colon, is a common digestive disorder that involves both the small intestine and the large bowel. This disorder is characterized by abdominal pain, constipation, bloating, nausea, headache, and/or diarrhea. The spastic colon type of this syndrome is characterized by variable bowel movements and abdominal pain that is associated with periodic constipation or diarrhea. Those patients with irritable bowel syndrome who have painless diarrhea may experience an urgent need to defecate upon arising. (For more information on this disorder, choose “Irritable Bowel Syndrome” as your search term in the Rare Disease Database.)Intestinal pseudoobstruction is a gastrointestinal disorder characterized by a lack of motility of the intestine. This condition resembles a true obstruction although there is no evidence of any physical obstruction. Symptoms may include constipation, colicky pain, vomiting, and weight loss. Intestinal pseudoobstruction may also affect speech, muscle activity, and the nervous system. (For more information on this disorder, choose “Intestinal Pseudoobstruction, Intestinal” as your search term in the Rare Disease Database.)Giant hypertrophic gastritis is a chronic disorder characterized by the presence of large, coiled ridges or folds, in the inner wall of the stomach. Symptoms include abdominal pain or discomfort and tenderness in the upper middle region of the abdomen. Other symptoms may include a profound loss of appetite, nausea, vomiting, and diarrhea. (For more information on this disorder, choose “Giant Hypertrophic Gastritis” as your search term in the Rare Disease Database.)Acquired immune deficiency syndrome (AIDS) is an immunosuppressive disorder caused by infection with the human immunodeficiency virus (HIV). The immune deficiency is a result of a viral infection and the destruction of specific T cells. Initially HIV infection is characterized by a period without symptoms. This may be followed by the development of swollen lymph nodes (lymphadenopathy). Eventually most people with acquired immune deficiency syndrome experience a progression of symptoms that occur as a result of a compromised immune system. When a person with AIDS has an intestinal infection with Mycobacterium avium intracellulare, the symptoms may be confused with those of Whipple disease. (For more information on this disorder, choose “AIDS” as your search term in the Rare Disease Database.)
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Diagnosis of Whipple Disease
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The standard diagnostic approach is to study a tissue sample (biopsy) from the small intestine. Blood testing can determine whether anemia is present. Confirmation of diagnosis can be achieved either by electron microscopy or by a test known as polymerase chain reaction (PCR) analysis, which detects the DNA of T. whippelii.
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Diagnosis of Whipple Disease. The standard diagnostic approach is to study a tissue sample (biopsy) from the small intestine. Blood testing can determine whether anemia is present. Confirmation of diagnosis can be achieved either by electron microscopy or by a test known as polymerase chain reaction (PCR) analysis, which detects the DNA of T. whippelii.
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Therapies of Whipple Disease
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TreatmentIf not treated, Whipple disease can become life-threatening. It can be cured, however, with antibiotics. Various types and combinations of antibiotics have been used. Relapses may occur, either during therapy or after it has been completed. For that reason, antibiotic therapy may be extended over a long period of time (up to a year or longer). One combination of antibiotics considered to be effective is trimethoprim-sulfamethoxazole, but there are also several alternatives. If symptoms reappear during therapy, a change in the antibiotic regimen may be needed. Complete healing may require as long as two years.Some patients with severe intestinal malabsorption caused by Whipple disease may need the intravenous administration of fluids and electrolytes. Other patients may require iron, folate supplements, vitamin D, and calcium. Since most patients with this disorder suffer from malnutrition, the recommended diet is usually high in calories and protein. Both diet and antibiotics must be monitored regularly by a physician.While the symptoms of WD may improve rapidly with long-term antibiotic therapy, biopsy may reveal bacteria in the small intestine for up to two years. Whipple's disease has been completely reversed by antibiotic therapy. The absence of bacilliform (rod shaped bacteria) in a biopsy sample of the small bowel typically suggests remission and possible cure.
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Therapies of Whipple Disease. TreatmentIf not treated, Whipple disease can become life-threatening. It can be cured, however, with antibiotics. Various types and combinations of antibiotics have been used. Relapses may occur, either during therapy or after it has been completed. For that reason, antibiotic therapy may be extended over a long period of time (up to a year or longer). One combination of antibiotics considered to be effective is trimethoprim-sulfamethoxazole, but there are also several alternatives. If symptoms reappear during therapy, a change in the antibiotic regimen may be needed. Complete healing may require as long as two years.Some patients with severe intestinal malabsorption caused by Whipple disease may need the intravenous administration of fluids and electrolytes. Other patients may require iron, folate supplements, vitamin D, and calcium. Since most patients with this disorder suffer from malnutrition, the recommended diet is usually high in calories and protein. Both diet and antibiotics must be monitored regularly by a physician.While the symptoms of WD may improve rapidly with long-term antibiotic therapy, biopsy may reveal bacteria in the small intestine for up to two years. Whipple's disease has been completely reversed by antibiotic therapy. The absence of bacilliform (rod shaped bacteria) in a biopsy sample of the small bowel typically suggests remission and possible cure.
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Overview of Wieacker Syndrome
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Wieacker syndrome is a rare, slowly progressive, genetic disorder present at birth and characterized by deformities of the joints of the feet (contracture), muscle degeneration (atrophy), mild intellectual disability and an impaired ability to move certain muscles of the eyes, face and tongue. Wieacker syndrome is inherited as an X-linked recessive trait.
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Overview of Wieacker Syndrome. Wieacker syndrome is a rare, slowly progressive, genetic disorder present at birth and characterized by deformities of the joints of the feet (contracture), muscle degeneration (atrophy), mild intellectual disability and an impaired ability to move certain muscles of the eyes, face and tongue. Wieacker syndrome is inherited as an X-linked recessive trait.
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Symptoms of Wieacker Syndrome
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Symptoms of Wieacker syndrome include stiffening of the muscles and joints of the feet (contracture), slowly progressive atrophy of certain muscles of the legs and arms, and mild intellectual disability. Other symptoms are impairment or inability to move the eyes despite the wish to do so, and impairment in the use of face and tongue muscles. In some cases, affected individuals may have droopy eyelids (ptosis), crossed eyes (strabismus), and farsightedness (hyperopia). Abnormal curvature of the spine may also occur (kyphoscoliosis).
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Symptoms of Wieacker Syndrome. Symptoms of Wieacker syndrome include stiffening of the muscles and joints of the feet (contracture), slowly progressive atrophy of certain muscles of the legs and arms, and mild intellectual disability. Other symptoms are impairment or inability to move the eyes despite the wish to do so, and impairment in the use of face and tongue muscles. In some cases, affected individuals may have droopy eyelids (ptosis), crossed eyes (strabismus), and farsightedness (hyperopia). Abnormal curvature of the spine may also occur (kyphoscoliosis).
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Causes of Wieacker Syndrome
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Wieacker syndrome is inherited as an X-linked recessive trait. It is caused by a defect in the ZC4H2 gene, located on a particular site of the X chromosome (Xq13-q21). The ZC4H2 gene is expressed in the synapses of the nervous system and plays an important role during embryonic development of the central and peripheral nervous system.
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. For example, “chromosome Xq13-q21″ refers to a region on the long arm of the X chromosome between bands 13 and 21. The numbered bands specify the location of the thousands of genes that are present on each chromosome.X-linked recessive genetic disorders, such as Wieacker syndrome, are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes, but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. 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. 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.
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Causes of Wieacker Syndrome. Wieacker syndrome is inherited as an X-linked recessive trait. It is caused by a defect in the ZC4H2 gene, located on a particular site of the X chromosome (Xq13-q21). The ZC4H2 gene is expressed in the synapses of the nervous system and plays an important role during embryonic development of the central and peripheral nervous system.
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. For example, “chromosome Xq13-q21″ refers to a region on the long arm of the X chromosome between bands 13 and 21. The numbered bands specify the location of the thousands of genes that are present on each chromosome.X-linked recessive genetic disorders, such as Wieacker syndrome, are conditions caused by an abnormal gene on the X chromosome. Females have two X chromosomes, but one of the X chromosomes is “turned off” and all of the genes on that chromosome are inactivated. Females who have a disease gene present on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms of the disorder because it is usually the X chromosome with the abnormal gene that is “turned off”. A male has one X chromosome and if he inherits an X chromosome that contains a disease gene, he will develop the disease. 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. 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.
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Affects of Wieacker Syndrome
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The prevalence of Wieacker syndrome is not known. Wieacker syndrome usually affects males, but some carrier females show mild manifestations of the disorder. As of 2015, the syndrome has been reported in 5 families. ZC4H2 gene mutations have also been identified in 3 sporadic patients who presented more or less severe intellectual disability and congenital contractures of multiple joints, at least equinovarus of the feet, associated with neurological symptoms such as muscle weakness, spasticity, seizures and ptosis. In one of the families, those affected had neonatal respiratory distress responsible for early death. Wieacker syndrome is therefore now considered to be part of a wider phenotype consisting of arthrogryposis multiplex congenita (congenital multiple joint contractures) and intellectual disability, caused by ZC4H2 gene mutations.
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Affects of Wieacker Syndrome. The prevalence of Wieacker syndrome is not known. Wieacker syndrome usually affects males, but some carrier females show mild manifestations of the disorder. As of 2015, the syndrome has been reported in 5 families. ZC4H2 gene mutations have also been identified in 3 sporadic patients who presented more or less severe intellectual disability and congenital contractures of multiple joints, at least equinovarus of the feet, associated with neurological symptoms such as muscle weakness, spasticity, seizures and ptosis. In one of the families, those affected had neonatal respiratory distress responsible for early death. Wieacker syndrome is therefore now considered to be part of a wider phenotype consisting of arthrogryposis multiplex congenita (congenital multiple joint contractures) and intellectual disability, caused by ZC4H2 gene mutations.
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Related disorders of Wieacker Syndrome
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Symptoms of the following disorders can be similar to those of Wieacker Syndrome. Comparisons may be useful for a differential diagnosis:Apraxia is a disorder of brain function characterized by the inability to perform learned movement on command, even though the command is understood and there is a willingness to perform the movement. The affected individual has the physical ability to move, but cannot. Apraxia is caused by a lesion in the neural pathways of the brain that contain the learned patterns of movement. It is often a symptom of other neurological disorders. (For more information on this disorder, choose “Apraxia” as your search term in the Rare Disease Database.)
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Related disorders of Wieacker Syndrome. Symptoms of the following disorders can be similar to those of Wieacker Syndrome. Comparisons may be useful for a differential diagnosis:Apraxia is a disorder of brain function characterized by the inability to perform learned movement on command, even though the command is understood and there is a willingness to perform the movement. The affected individual has the physical ability to move, but cannot. Apraxia is caused by a lesion in the neural pathways of the brain that contain the learned patterns of movement. It is often a symptom of other neurological disorders. (For more information on this disorder, choose “Apraxia” as your search term in the Rare Disease Database.)
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Wieacker Syndrome
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Diagnosis of Wieacker Syndrome
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In some instances in the history of the family in which the syndrome was first described, the syndrome was present at birth.
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Diagnosis of Wieacker Syndrome. In some instances in the history of the family in which the syndrome was first described, the syndrome was present at birth.
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Wieacker Syndrome
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Therapies of Wieacker Syndrome
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TreatmentTreatment is symptomatic and supportive. The syndrome is little understood at this time.Physical therapy, surgery, speech therapy, and special education can be of benefit, especially if started as early as possible. Genetic counseling may be of benefit for the families of children with Wieacker syndrome.
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Therapies of Wieacker Syndrome. TreatmentTreatment is symptomatic and supportive. The syndrome is little understood at this time.Physical therapy, surgery, speech therapy, and special education can be of benefit, especially if started as early as possible. Genetic counseling may be of benefit for the families of children with Wieacker syndrome.
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Overview of Wiedemann Rautenstrauch Syndrome
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Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a very rare genetic disorder characterized by an aged appearance at birth (old man look) growth delays before and after birth (prenatal and postnatal growth retardation), and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). It is anticipated that most individuals with WRS have decreased life expectancy. There are few individuals who have lived well in to their teens and even fewer still alive in their 20s. WRS represents a complex of symptoms and signs with an unknown cause, and pathogenesis remains distinct enough to allow a secure diagnosis. WRS is inherited as an autosomal recessive trait, as several pairs of siblings have been reported in families with unaffected parents. Few of the parents were related by blood (consanguineous).
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Overview of Wiedemann Rautenstrauch Syndrome. Wiedemann-Rautenstrauch syndrome (WRS), also known as neonatal progeroid syndrome, is a very rare genetic disorder characterized by an aged appearance at birth (old man look) growth delays before and after birth (prenatal and postnatal growth retardation), and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). It is anticipated that most individuals with WRS have decreased life expectancy. There are few individuals who have lived well in to their teens and even fewer still alive in their 20s. WRS represents a complex of symptoms and signs with an unknown cause, and pathogenesis remains distinct enough to allow a secure diagnosis. WRS is inherited as an autosomal recessive trait, as several pairs of siblings have been reported in families with unaffected parents. Few of the parents were related by blood (consanguineous).
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Symptoms of Wiedemann Rautenstrauch Syndrome
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WRS is characterized by an aged appearance at birth and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). As a result, the skin may appear unusually thin, fragile, dry, shiny, wrinkled, and aged. Certain veins and muscles may be abnormally prominent, particularly those of the forehead. For unknown reasons, as affected infants age, abnormal deposits of fat may accumulate under the skin (subcutaneous) in lower (caudal) areas of the body, particularly around the buttocks, the areas around the genitals and the anus (anogenital area), and the area between the ribs and the hips (flanks). In addition, in infants and children with the disorder, the abdomen may appear unusually large and prominent.In individuals with WRS, growth delays may occur before birth (intrauterine growth retardation), particularly during the last three months (third trimester) of fetal development. The growth delays will continue well after birth (postnatal). Patients with WRS also experience poor weight gain, and failure to thrive through their lifetime. In addition, in some cases, affected infants may experience swallowing (dysphagia) and feeding difficulties that may contribute to growth delays and failure to thrive.Progressive neurological deterioration may occur in WRS. The specific symptoms may vary from person to person as affected individuals may not have all of the symptoms listed below.Infants and children with WRS also have distinctive abnormalities of the head and face (craniofacial). In many affected individuals, the soft spot in the front of the skull (anterior) may be abnormally large and wide, and its closure may be unusually delayed. The fibrous gaps between other bones in the skull (cranial sutures) may also be abnormally wide. In addition, in infants with the disorder, bones of the forehead (frontal bones) and the sides of the skull (parietal bones) are abnormally prominent (frontal and bi-parietal bossing), while the facial bones are unusually small and underdeveloped (hypoplastic).Such abnormalities may cause the head to appear unusually large (pseudohydrocephalus). In affected infants and children, distinctive facial abnormalities may include an unusually small mouth (microstomia); a prominent chin, and low-set ears that are abnormally angled toward the back of the head (posteriorly angulated). Facial features typically appear unusually small when compared with the large forehead and sides of the skull. In addition, affected infants may have an unusually small, distinctively “beak-shaped” nose that becomes more pronounced with advancing age.In most infants and children with WRS, additional craniofacial abnormalities are also present. Affected infants may have two to four front teeth (neonatal incisors), which fall out during the course of early infancy. Subsequent tooth development (dentition) is delayed and impaired. In addition, in infants and children with the disorder, the lower eyelids may droop or turn outward (ectropion), exposing the thin, delicate mucous membranes that line the eyelids as well as a portion of the eyeballs (conjunctivae). In one patient, spastic entropion, a condition in which the eyelid turns inward so that the eyelashes and skin rub against the eye surface, was also described. An interesting feature in a few cases is that the lower eyelids may cover more than the lower half of the eyeball as if the eyelids are situated higher than expected. Affected infants and children may also have unusually sparse scalp hair, eyebrows, and eyelashes. (hypotrichosis). In a family with three affected siblings, various eye abnormalities including cataract, cloudy cornea, perforation of cornea, and microphthalmia (unusually small size of the eye) also were noted.Infants and children with WRS may also have distinctive abnormalities affecting the hands, feet, arms, and legs (extremities). The arms and legs are abnormally thin, the hands and feet are disproportionately large; and the fingers and toes are long with unusually small, incompletely developed (atrophic) or thickened (dystrophic) nails. The joints are thick and rigid, especially in the shoulders, elbows and knees. Recent MRI (magnetic resonance imaging) studies have confirmed the presence of normal amounts of subcutaneous truncal fat, and marked loss of fat from the face and distal extremities. Bone thinning (osteopenia) may predispose to bony fractures. Bone progenitor cell transformation to bone (osteoblasts) and cartilage cells (chondrocytes) are also impaired. The lack of cellular differentiation capacity in WRS patients may be responsible for the clinical appearance and symptoms of this rare disorder.Most infants and children with the disorder also have varying degrees of intellectual disability, which may range from mild to severe. However, a few children have demonstrated near normal mental development. During infancy, affected individuals may begin to experience progressive neurological and neuromuscular abnormalities. In most patients, there are severe delays in the acquisition of skills requiring the coordination of physical and mental activities (psychomotor retardation). In addition, in many cases, infants and children with the disorder lack head control, exhibit diminished muscle tone (hypotonia), and have an impaired ability to coordinate voluntary movements of the chest and abdominal areas (truncal ataxia). For example, they may have difficulty controlling the range of movements during certain muscular actions and may experience rhythmic, involuntary tremors when performing certain movements (intention tremor). Infants and children with the disorder may also experience rapid, involuntary, horizontal movements of the eyes (horizontal nystagmus) and limited clearness (acuity) of vision. Infants may have dysphonic, horse cry and older children may have an unusual high-pitched voice.In addition, investigators have reported that neurological deterioration observed in a few individuals with WRS may be associated with loss of the myelin sheath from nerve fibers (demyelization) within the white substance of the brain (e.g., pure sudanophilic leukodystrophy). Myelin is a whitish fatty substance that forms a protective wrapping or “sheath” around certain nerve fibers (axons) and serves as an electrical insulator, enabling the effective transmission of nerve impulses. “White substance” within the brain and spinal cord (central nervous system) primarily consists of bundles of myelinated nerve fibers. The majority of patients with WRS did not have leukodystrophy at the age ascertained. Dandy Walker malformation and ventriculomegaly, basal ganglia calcification, and agenesis of corpus callosum were reported. The lack of subcutaneous fat tissue has prompted researchers to compare WRS with generalized lipodystrophy (Berardinelli) syndrome. Laboratory studies, however, in those cases examined, have shown no elevation of fasting glucose, lipids, or insulin, as would be expected in Berardinelli syndrome. A few patients however, had elevated triglyceride levels. Fat pads are localized at the flank, rather than at the buttocks, which is specific for this syndrome, but also can be seen in carbohydrate deficient glycoprotein syndrome (CDG). Individuals with WRS may also develop abnormal side-to-side curvature of the spine (scoliosis). In addition, infants and children with WRS are often prone to recurrent respiratory infections, which may result in life-threatening complications.In one of the few cases where post mortem pathology was performed, an almost total absence of the mesentery, a tissue that anchors the small intestines to the back of the abdominal wall, and absence of the mesocolon, the tissue that secures the transverse portion of the large intestines, were found.
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Symptoms of Wiedemann Rautenstrauch Syndrome. WRS is characterized by an aged appearance at birth and deficiency or absence of the layer of fat under the skin (subcutaneous lipoatrophy). As a result, the skin may appear unusually thin, fragile, dry, shiny, wrinkled, and aged. Certain veins and muscles may be abnormally prominent, particularly those of the forehead. For unknown reasons, as affected infants age, abnormal deposits of fat may accumulate under the skin (subcutaneous) in lower (caudal) areas of the body, particularly around the buttocks, the areas around the genitals and the anus (anogenital area), and the area between the ribs and the hips (flanks). In addition, in infants and children with the disorder, the abdomen may appear unusually large and prominent.In individuals with WRS, growth delays may occur before birth (intrauterine growth retardation), particularly during the last three months (third trimester) of fetal development. The growth delays will continue well after birth (postnatal). Patients with WRS also experience poor weight gain, and failure to thrive through their lifetime. In addition, in some cases, affected infants may experience swallowing (dysphagia) and feeding difficulties that may contribute to growth delays and failure to thrive.Progressive neurological deterioration may occur in WRS. The specific symptoms may vary from person to person as affected individuals may not have all of the symptoms listed below.Infants and children with WRS also have distinctive abnormalities of the head and face (craniofacial). In many affected individuals, the soft spot in the front of the skull (anterior) may be abnormally large and wide, and its closure may be unusually delayed. The fibrous gaps between other bones in the skull (cranial sutures) may also be abnormally wide. In addition, in infants with the disorder, bones of the forehead (frontal bones) and the sides of the skull (parietal bones) are abnormally prominent (frontal and bi-parietal bossing), while the facial bones are unusually small and underdeveloped (hypoplastic).Such abnormalities may cause the head to appear unusually large (pseudohydrocephalus). In affected infants and children, distinctive facial abnormalities may include an unusually small mouth (microstomia); a prominent chin, and low-set ears that are abnormally angled toward the back of the head (posteriorly angulated). Facial features typically appear unusually small when compared with the large forehead and sides of the skull. In addition, affected infants may have an unusually small, distinctively “beak-shaped” nose that becomes more pronounced with advancing age.In most infants and children with WRS, additional craniofacial abnormalities are also present. Affected infants may have two to four front teeth (neonatal incisors), which fall out during the course of early infancy. Subsequent tooth development (dentition) is delayed and impaired. In addition, in infants and children with the disorder, the lower eyelids may droop or turn outward (ectropion), exposing the thin, delicate mucous membranes that line the eyelids as well as a portion of the eyeballs (conjunctivae). In one patient, spastic entropion, a condition in which the eyelid turns inward so that the eyelashes and skin rub against the eye surface, was also described. An interesting feature in a few cases is that the lower eyelids may cover more than the lower half of the eyeball as if the eyelids are situated higher than expected. Affected infants and children may also have unusually sparse scalp hair, eyebrows, and eyelashes. (hypotrichosis). In a family with three affected siblings, various eye abnormalities including cataract, cloudy cornea, perforation of cornea, and microphthalmia (unusually small size of the eye) also were noted.Infants and children with WRS may also have distinctive abnormalities affecting the hands, feet, arms, and legs (extremities). The arms and legs are abnormally thin, the hands and feet are disproportionately large; and the fingers and toes are long with unusually small, incompletely developed (atrophic) or thickened (dystrophic) nails. The joints are thick and rigid, especially in the shoulders, elbows and knees. Recent MRI (magnetic resonance imaging) studies have confirmed the presence of normal amounts of subcutaneous truncal fat, and marked loss of fat from the face and distal extremities. Bone thinning (osteopenia) may predispose to bony fractures. Bone progenitor cell transformation to bone (osteoblasts) and cartilage cells (chondrocytes) are also impaired. The lack of cellular differentiation capacity in WRS patients may be responsible for the clinical appearance and symptoms of this rare disorder.Most infants and children with the disorder also have varying degrees of intellectual disability, which may range from mild to severe. However, a few children have demonstrated near normal mental development. During infancy, affected individuals may begin to experience progressive neurological and neuromuscular abnormalities. In most patients, there are severe delays in the acquisition of skills requiring the coordination of physical and mental activities (psychomotor retardation). In addition, in many cases, infants and children with the disorder lack head control, exhibit diminished muscle tone (hypotonia), and have an impaired ability to coordinate voluntary movements of the chest and abdominal areas (truncal ataxia). For example, they may have difficulty controlling the range of movements during certain muscular actions and may experience rhythmic, involuntary tremors when performing certain movements (intention tremor). Infants and children with the disorder may also experience rapid, involuntary, horizontal movements of the eyes (horizontal nystagmus) and limited clearness (acuity) of vision. Infants may have dysphonic, horse cry and older children may have an unusual high-pitched voice.In addition, investigators have reported that neurological deterioration observed in a few individuals with WRS may be associated with loss of the myelin sheath from nerve fibers (demyelization) within the white substance of the brain (e.g., pure sudanophilic leukodystrophy). Myelin is a whitish fatty substance that forms a protective wrapping or “sheath” around certain nerve fibers (axons) and serves as an electrical insulator, enabling the effective transmission of nerve impulses. “White substance” within the brain and spinal cord (central nervous system) primarily consists of bundles of myelinated nerve fibers. The majority of patients with WRS did not have leukodystrophy at the age ascertained. Dandy Walker malformation and ventriculomegaly, basal ganglia calcification, and agenesis of corpus callosum were reported. The lack of subcutaneous fat tissue has prompted researchers to compare WRS with generalized lipodystrophy (Berardinelli) syndrome. Laboratory studies, however, in those cases examined, have shown no elevation of fasting glucose, lipids, or insulin, as would be expected in Berardinelli syndrome. A few patients however, had elevated triglyceride levels. Fat pads are localized at the flank, rather than at the buttocks, which is specific for this syndrome, but also can be seen in carbohydrate deficient glycoprotein syndrome (CDG). Individuals with WRS may also develop abnormal side-to-side curvature of the spine (scoliosis). In addition, infants and children with WRS are often prone to recurrent respiratory infections, which may result in life-threatening complications.In one of the few cases where post mortem pathology was performed, an almost total absence of the mesentery, a tissue that anchors the small intestines to the back of the abdominal wall, and absence of the mesocolon, the tissue that secures the transverse portion of the large intestines, were found.
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Wiedemann Rautenstrauch Syndrome
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nord_1296_2
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Causes of Wiedemann Rautenstrauch Syndrome
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WRS is most likely inherited as an autosomal recessive genetic condition. Several siblings with WRS have been reported in unrelated families.Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person is a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to 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 is 25%. The risk is the same for males and females.Some individuals with WRS have had parents, who were related by blood (consanguineous).All individuals carry several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than non-consanguineous parents to carry the same abnormal gene, which increases the risk to have children with a rare recessive genetic disorder.The specific underlying defect responsible for the disorder remains unknown. However, some researchers suggest that disturbances in bone maturation and hormonal and fatty (lipid) metabolism may play some role.
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Causes of Wiedemann Rautenstrauch Syndrome. WRS is most likely inherited as an autosomal recessive genetic condition. Several siblings with WRS have been reported in unrelated families.Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual receives one normal gene and one gene for the disease, the person is a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to 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 is 25%. The risk is the same for males and females.Some individuals with WRS have had parents, who were related by blood (consanguineous).All individuals carry several abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than non-consanguineous parents to carry the same abnormal gene, which increases the risk to have children with a rare recessive genetic disorder.The specific underlying defect responsible for the disorder remains unknown. However, some researchers suggest that disturbances in bone maturation and hormonal and fatty (lipid) metabolism may play some role.
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Wiedemann Rautenstrauch Syndrome
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nord_1296_3
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Affects of Wiedemann Rautenstrauch Syndrome
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WRS is an extremely rare genetic disorder that appears to affect males and females relatively equally. WRS has been observed in various ethnic and racial groups. The disorder was initially described as a distinct entity in 1979 (Wiedemann HR) based upon observation of two unrelated individuals as well as previous reports of two affected sisters in 1977 (Rautenstrauch T). More than 35 affected individuals have been reported in the medical literature to date.
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Affects of Wiedemann Rautenstrauch Syndrome. WRS is an extremely rare genetic disorder that appears to affect males and females relatively equally. WRS has been observed in various ethnic and racial groups. The disorder was initially described as a distinct entity in 1979 (Wiedemann HR) based upon observation of two unrelated individuals as well as previous reports of two affected sisters in 1977 (Rautenstrauch T). More than 35 affected individuals have been reported in the medical literature to date.
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Wiedemann Rautenstrauch Syndrome
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Related disorders of Wiedemann Rautenstrauch Syndrome
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Symptoms of the following disorders may be similar to those of Wiedemann-Rautenstrauch syndrome. Comparisons may be useful for a differential diagnosis:WRS shares some common clinical characteristics with Hutchinson-Gilford progeria syndrome (HGPS). Similarly there was no telomere length shortening in skin fibroblast in a patient with WRS. This result differs from those observed in HGPS. HGPS is a very rare progressive fatal disorder of childhood characterized by premature aging (progeria), growth delays occurring in the first year of life resulting in short stature and low weight, deterioration of the layer of fat beneath the skin (subcutaneous adipose tissue), and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated nonhealing fractures, a progressive aged appearance of the skin, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. Most affected individuals experience premature and widespread thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. It is a recent discovery, that a mutation in a single gene called Lamin A (LMNA), is responsible for HGPS. This particular gene makes a protein necessary to hold the center (nucleus) of a cell together. However, when the LMNA gene was analyzed in a few cases of WRS, there was no abnormality found. Molecular genetic testing of (Lamin A) LMNA, the only gene known to be associated with HGPS, is available on a clinical basis. All cases are sporadic. (For more information on this disorder, choose “Hutchinson-Gilford progeria” as your search term in the Rare Disease Database.)Hallerman-Streiff syndrome, a rare genetic disorder, is characterized by distinctive craniofacial malformations including an abnormally small head (microcephaly) that is unusually wide (brachycephaly) with a prominent forehead (frontal bossing); an underdeveloped lower jaw (hypoplastic mandible), an unusually small mouth (microstomia); and/or a “beak-shaped” nose. The disorder is also characterized by proportionate short stature (dwarfism); abnormalities of the eyes; malformations of the teeth; and/or other abnormalities. Eye (ocular) abnormalities may include unusually small eyes (microphthalmia); clouding of the lenses of the eyes at birth (congenital cataracts), rapid, involuntary eye movements (nystagmus), crossing of the eyes (strabismus), decreased clarity of vision (visual acuity), and/or other ocular abnormalities. Dental defects may include the presence of certain teeth at birth (neonatal teeth), improper development of tooth enamel (enamel dysplasia); and/or absence (hypodontia or partial adontia), malformation, and/or improper alignment of certain teeth. Individuals with Hallerman-Streiff syndrome typically have normal intelligence. In most patients, the disorder appears to occur randomly for unknown reasons (sporadically). In other individuals, Hallermann-Streiff syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Hallermann Streiff” as your search term in the Rare Disease Database.)De Barsy syndrome (also known as progeroid syndrome of De Barsy) is an extremely rare genetic disorder that is apparent at birth. The disorder is characterized by abnormal looseness of the skin (cutis laxa); an aged (progeroid) appearance, clouding of the lenses of the eyes (cataracts); continual, involuntary writhing movements, particularly of the arms and legs (athetosis) and/or short stature. Affected infants and children may also have abnormalities of the head and facial area including an unusually small head (microcephaly) with a prominent forehead (frontal bossing); large, misshapen (dysplastic) ears; thin lips, and/or sparse scalp hair. Additional characteristics often associated with the disorder may include diminished muscle tone (hypotonia), psychomotor retardation, and intellectual disability. De Barsy syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “De Barsy” as your search term in the Rare Disease Database.)Cockayne syndrome is a very rare genetic disorder characterized by growth disability, abnormal sensitivity to sunlight (photosensitivity), a prematurely aged (progeroid) appearance, and/or other abnormalities. In the classical form of Cockayne syndrome (Type I), the symptoms are progressive and typically become apparent within the first year of life. In early onset Cockayne syndrome (Type II), associated symptoms and physical findings are apparent at birth (congenital). Affected individuals have distinctive craniofacial abnormalities including an unusually small head (microcephaly), loss of fat underneath the skin, sunken eyes, malformed ears, and a thin, beaked nose. Such abnormalities contribute to a prematurely aged appearance. Individuals with the disorder also exhibit short stature, progressive loss of vision due to degeneration of the nerve-rich membrane lining the eyes (retina), extreme sensitivity to sunlight (photosensitivity), and/or neurological degeneration including progressive intellectual disability, movement disturbances, deafness, and loss of intellectual abilities (dementia). Some affected individuals may exhibit premature thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. Cockayne syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Cockayne” as your search term in the Rare Disease Database.)There are additional congenital disorders that may be characterized by growth delays, progeroid appearance, craniofacial malformations, intellectual disability, progressive neurological and neuromuscular symptoms, and/or other abnormalities similar to those occurring in association with Wiedemann-Rautenstrauch syndrome. Such disorders usually have other symptoms or physical findings that may differentiate them from Wiedemann-Rautenstrauch syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Wiedemann Rautenstrauch Syndrome. Symptoms of the following disorders may be similar to those of Wiedemann-Rautenstrauch syndrome. Comparisons may be useful for a differential diagnosis:WRS shares some common clinical characteristics with Hutchinson-Gilford progeria syndrome (HGPS). Similarly there was no telomere length shortening in skin fibroblast in a patient with WRS. This result differs from those observed in HGPS. HGPS is a very rare progressive fatal disorder of childhood characterized by premature aging (progeria), growth delays occurring in the first year of life resulting in short stature and low weight, deterioration of the layer of fat beneath the skin (subcutaneous adipose tissue), and characteristic craniofacial abnormalities including an abnormally small face, underdeveloped jaw (micrognathia), unusually prominent eyes, and/or a small, “beak-like” nose. In addition, during the first year or two of life, scalp hair, eyebrows, and eyelashes may become sparse, and veins of the scalp may become unusually prominent. Additional symptoms and physical findings may include joint stiffness, repeated nonhealing fractures, a progressive aged appearance of the skin, delays in tooth eruption (dentition), and/or malformation and crowding of the teeth. Individuals with the disorder typically have normal intelligence. Most affected individuals experience premature and widespread thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. It is a recent discovery, that a mutation in a single gene called Lamin A (LMNA), is responsible for HGPS. This particular gene makes a protein necessary to hold the center (nucleus) of a cell together. However, when the LMNA gene was analyzed in a few cases of WRS, there was no abnormality found. Molecular genetic testing of (Lamin A) LMNA, the only gene known to be associated with HGPS, is available on a clinical basis. All cases are sporadic. (For more information on this disorder, choose “Hutchinson-Gilford progeria” as your search term in the Rare Disease Database.)Hallerman-Streiff syndrome, a rare genetic disorder, is characterized by distinctive craniofacial malformations including an abnormally small head (microcephaly) that is unusually wide (brachycephaly) with a prominent forehead (frontal bossing); an underdeveloped lower jaw (hypoplastic mandible), an unusually small mouth (microstomia); and/or a “beak-shaped” nose. The disorder is also characterized by proportionate short stature (dwarfism); abnormalities of the eyes; malformations of the teeth; and/or other abnormalities. Eye (ocular) abnormalities may include unusually small eyes (microphthalmia); clouding of the lenses of the eyes at birth (congenital cataracts), rapid, involuntary eye movements (nystagmus), crossing of the eyes (strabismus), decreased clarity of vision (visual acuity), and/or other ocular abnormalities. Dental defects may include the presence of certain teeth at birth (neonatal teeth), improper development of tooth enamel (enamel dysplasia); and/or absence (hypodontia or partial adontia), malformation, and/or improper alignment of certain teeth. Individuals with Hallerman-Streiff syndrome typically have normal intelligence. In most patients, the disorder appears to occur randomly for unknown reasons (sporadically). In other individuals, Hallermann-Streiff syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Hallermann Streiff” as your search term in the Rare Disease Database.)De Barsy syndrome (also known as progeroid syndrome of De Barsy) is an extremely rare genetic disorder that is apparent at birth. The disorder is characterized by abnormal looseness of the skin (cutis laxa); an aged (progeroid) appearance, clouding of the lenses of the eyes (cataracts); continual, involuntary writhing movements, particularly of the arms and legs (athetosis) and/or short stature. Affected infants and children may also have abnormalities of the head and facial area including an unusually small head (microcephaly) with a prominent forehead (frontal bossing); large, misshapen (dysplastic) ears; thin lips, and/or sparse scalp hair. Additional characteristics often associated with the disorder may include diminished muscle tone (hypotonia), psychomotor retardation, and intellectual disability. De Barsy syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “De Barsy” as your search term in the Rare Disease Database.)Cockayne syndrome is a very rare genetic disorder characterized by growth disability, abnormal sensitivity to sunlight (photosensitivity), a prematurely aged (progeroid) appearance, and/or other abnormalities. In the classical form of Cockayne syndrome (Type I), the symptoms are progressive and typically become apparent within the first year of life. In early onset Cockayne syndrome (Type II), associated symptoms and physical findings are apparent at birth (congenital). Affected individuals have distinctive craniofacial abnormalities including an unusually small head (microcephaly), loss of fat underneath the skin, sunken eyes, malformed ears, and a thin, beaked nose. Such abnormalities contribute to a prematurely aged appearance. Individuals with the disorder also exhibit short stature, progressive loss of vision due to degeneration of the nerve-rich membrane lining the eyes (retina), extreme sensitivity to sunlight (photosensitivity), and/or neurological degeneration including progressive intellectual disability, movement disturbances, deafness, and loss of intellectual abilities (dementia). Some affected individuals may exhibit premature thickening and loss of elasticity of artery walls (arteriosclerosis), potentially resulting in life-threatening complications. Cockayne syndrome is inherited as an autosomal recessive genetic trait. (For more information on this disorder, choose “Cockayne” as your search term in the Rare Disease Database.)There are additional congenital disorders that may be characterized by growth delays, progeroid appearance, craniofacial malformations, intellectual disability, progressive neurological and neuromuscular symptoms, and/or other abnormalities similar to those occurring in association with Wiedemann-Rautenstrauch syndrome. Such disorders usually have other symptoms or physical findings that may differentiate them from Wiedemann-Rautenstrauch syndrome. (For more information on these disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis of Wiedemann Rautenstrauch Syndrome
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In some cases, growth disability, macrocephaly, and/or other characteristic findings suggestive of Wiedemann-Rautenstrauch Syndrome may be detected before birth (prenatally) by ultrasound.In most patients, Wiedemann-Rautenstrauch syndrome is diagnosed shortly after birth, based upon a thorough clinical evaluation and identification of characteristic physical findings (e.g., short stature, characteristic craniofacial and skeletal malformations, absence or deficiency of subcutaneous fat, etc.). In some cases, specialized tests may also be conducted to detect certain abnormalities potentially associated with the disorder. For example, X-ray studies may reveal and/or confirm wide cranial sutures and/or other abnormalities of cranial bones. In addition, it is possible that computer-assisted tomography (CAT), magnetic resonance imaging (MRI), and/or other specialized tests may reveal widespread loss of the fatty coverings (myelin sheath) on nerve fibers (demyelination) within the white matter of the brain (pure sudanophilic leukodystrophy) or other abnormalities as described above.
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Diagnosis of Wiedemann Rautenstrauch Syndrome. In some cases, growth disability, macrocephaly, and/or other characteristic findings suggestive of Wiedemann-Rautenstrauch Syndrome may be detected before birth (prenatally) by ultrasound.In most patients, Wiedemann-Rautenstrauch syndrome is diagnosed shortly after birth, based upon a thorough clinical evaluation and identification of characteristic physical findings (e.g., short stature, characteristic craniofacial and skeletal malformations, absence or deficiency of subcutaneous fat, etc.). In some cases, specialized tests may also be conducted to detect certain abnormalities potentially associated with the disorder. For example, X-ray studies may reveal and/or confirm wide cranial sutures and/or other abnormalities of cranial bones. In addition, it is possible that computer-assisted tomography (CAT), magnetic resonance imaging (MRI), and/or other specialized tests may reveal widespread loss of the fatty coverings (myelin sheath) on nerve fibers (demyelination) within the white matter of the brain (pure sudanophilic leukodystrophy) or other abnormalities as described above.
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Therapies of Wiedemann Rautenstrauch Syndrome
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TreatmentThe treatment of Wiedemann-Rautenstrauch 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, specialists who assess and treat disorders of the nervous system (neurologists), physical therapists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for Wiedemann-Rautenstrauch syndrome are symptomatic and supportive. In some cases, if affected infants and children experience swallowing and feeding difficulties and cannot feed appropriately by mouth, a tube may be surgically inserted into the stomach or a portion of the small intestine (tube feeding) to help provide appropriate nourishment. In addition, affected infants and children should be carefully monitored to help guard against respiratory infections. Genetic counseling will be of benefit for affected individuals and their families.
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Therapies of Wiedemann Rautenstrauch Syndrome. TreatmentThe treatment of Wiedemann-Rautenstrauch 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, specialists who assess and treat disorders of the nervous system (neurologists), physical therapists, and/or other health care professionals may need to systematically and comprehensively plan an affected child's treatment.Specific therapies for Wiedemann-Rautenstrauch syndrome are symptomatic and supportive. In some cases, if affected infants and children experience swallowing and feeding difficulties and cannot feed appropriately by mouth, a tube may be surgically inserted into the stomach or a portion of the small intestine (tube feeding) to help provide appropriate nourishment. In addition, affected infants and children should be carefully monitored to help guard against respiratory infections. Genetic counseling will be of benefit for affected individuals and their families.
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Overview of Wiedemann-Steiner Syndrome
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Summary
Wiedemann-Steiner syndrome (WSS) is a rare genetic condition that can affect multiple organ systems. Many patients with this condition have symptoms including developmental delay, intellectual disability or autism and excessive hair growth in unusual places on the body (hypertrichosis). Characteristic facial features include a short distance between the upper and lower eyelid or down-slanting eyes (narrow or down-slanting palpebral fissures), a drooping upper eyelid over the eye (ptosis), wide-set eyes (hypertelorism), long eyelashes, thick eyebrows, wide nose (wide nasal bridge), deep-set nose (depressed nasal bridge), long vertical groove under the nose, low hairline, high palate, and dental/oral abnormalities. Additional findings can also be associated with the condition but are not always present. These anomalies may include growth delays, neurological abnormalities, muscular and skeletal differences, gastrointestinal differences, cardiac abnormalities, genitourinary anomalies, and endocrine problems. WSS is caused by a change in the KMT2A gene (previously known as the MLL gene). Introduction
Each patient with Wiedemann-Steiner syndrome can have very different symptoms making it difficult for physicians to accurately identify and diagnose patients. There are many conditions with similar symptoms, and there are no set diagnostic criteria for WSS. Therefore, WSS is much less likely to be diagnosed in patients without access to genetics providers or testing.
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Overview of Wiedemann-Steiner Syndrome. Summary
Wiedemann-Steiner syndrome (WSS) is a rare genetic condition that can affect multiple organ systems. Many patients with this condition have symptoms including developmental delay, intellectual disability or autism and excessive hair growth in unusual places on the body (hypertrichosis). Characteristic facial features include a short distance between the upper and lower eyelid or down-slanting eyes (narrow or down-slanting palpebral fissures), a drooping upper eyelid over the eye (ptosis), wide-set eyes (hypertelorism), long eyelashes, thick eyebrows, wide nose (wide nasal bridge), deep-set nose (depressed nasal bridge), long vertical groove under the nose, low hairline, high palate, and dental/oral abnormalities. Additional findings can also be associated with the condition but are not always present. These anomalies may include growth delays, neurological abnormalities, muscular and skeletal differences, gastrointestinal differences, cardiac abnormalities, genitourinary anomalies, and endocrine problems. WSS is caused by a change in the KMT2A gene (previously known as the MLL gene). Introduction
Each patient with Wiedemann-Steiner syndrome can have very different symptoms making it difficult for physicians to accurately identify and diagnose patients. There are many conditions with similar symptoms, and there are no set diagnostic criteria for WSS. Therefore, WSS is much less likely to be diagnosed in patients without access to genetics providers or testing.
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Symptoms of Wiedemann-Steiner Syndrome
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People with Wiedemann-Steiner syndrome can have a broad range of symptoms that affect many body systems. Not everyone will have all the symptoms mentioned below, and the body systems affected can differ from person to person. The symptoms may be present at birth but can also begin later during infancy or childhood.Signs of delayed growth and development can be low birthweight and failure to meet milestones in childhood, such as sitting, standing, walking and speech. Other symptoms can include feeding difficulties, short stature and early eruption of teeth. Some of the symptoms affecting the brain can include intellectual disability, abnormal brain MRI findings, low muscle tone (hypotonia) and more rarely, seizures. Many people with WSS have excessive hair growth on different parts of the body such as face, chest, back, elbows, thick eyebrows, unibrow and long eyelashes. Characteristic facial features include a short distance between the upper and lower eyelid or down-slanting eyes (narrow or down-slanting palpebral fissures), a drooping upper eyelid over the eye (ptosis), wide-set eyes (hypertelorism), wide nose (wide nasal bridge), deep-set nose (depressed nasal bridge), long vertical groove under the nose, low hairline, high palate and dental/oral abnormalities. Additional findings can also be associated with the condition but are not always present. These anomalies may include growth delays, muscular and skeletal differences, gastrointestinal differences, cardiac abnormalities, genitourinary anomalies and endocrine problems. Constipation is another symptom that can be seen commonly in individuals with this condition. Skeletal issues including a dimple on the lower back (sacral dimple), short fingers or toes, abnormally curved fingers, puffy hands or feet and issues with the spine (vertebrae) are also common in individuals with Wiedemann-Steiner syndrome. More rarely seen symptoms include issues affecting the eyes, heart, immune system, kidney, ear nose and throat (ENT), cleft palate, endocrine system (hormones) and autism spectrum disorder (ASD).
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Symptoms of Wiedemann-Steiner Syndrome. People with Wiedemann-Steiner syndrome can have a broad range of symptoms that affect many body systems. Not everyone will have all the symptoms mentioned below, and the body systems affected can differ from person to person. The symptoms may be present at birth but can also begin later during infancy or childhood.Signs of delayed growth and development can be low birthweight and failure to meet milestones in childhood, such as sitting, standing, walking and speech. Other symptoms can include feeding difficulties, short stature and early eruption of teeth. Some of the symptoms affecting the brain can include intellectual disability, abnormal brain MRI findings, low muscle tone (hypotonia) and more rarely, seizures. Many people with WSS have excessive hair growth on different parts of the body such as face, chest, back, elbows, thick eyebrows, unibrow and long eyelashes. Characteristic facial features include a short distance between the upper and lower eyelid or down-slanting eyes (narrow or down-slanting palpebral fissures), a drooping upper eyelid over the eye (ptosis), wide-set eyes (hypertelorism), wide nose (wide nasal bridge), deep-set nose (depressed nasal bridge), long vertical groove under the nose, low hairline, high palate and dental/oral abnormalities. Additional findings can also be associated with the condition but are not always present. These anomalies may include growth delays, muscular and skeletal differences, gastrointestinal differences, cardiac abnormalities, genitourinary anomalies and endocrine problems. Constipation is another symptom that can be seen commonly in individuals with this condition. Skeletal issues including a dimple on the lower back (sacral dimple), short fingers or toes, abnormally curved fingers, puffy hands or feet and issues with the spine (vertebrae) are also common in individuals with Wiedemann-Steiner syndrome. More rarely seen symptoms include issues affecting the eyes, heart, immune system, kidney, ear nose and throat (ENT), cleft palate, endocrine system (hormones) and autism spectrum disorder (ASD).
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Causes of Wiedemann-Steiner Syndrome
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Wiedemann-Steiner syndrome is caused by changes (pathogenic variants or mutations) in the KMT2A gene (previously known as the MLL gene). This gene plays a role in the regulation of early development and blood production. WSS follows autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to child is 50% for each pregnancy. The risk is the same for males and females.In most people with WSS, the change in the KMT2A gene that caused the disorder was not inherited from a parent but occurred spontaneously (de novo) in the individual with WSS. However, in a small number of patients reported in the medical literature, WSS was passed down from an affected parent to a child in an autosomal dominant manner.
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Causes of Wiedemann-Steiner Syndrome. Wiedemann-Steiner syndrome is caused by changes (pathogenic variants or mutations) in the KMT2A gene (previously known as the MLL gene). This gene plays a role in the regulation of early development and blood production. WSS follows autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a mutated gene is necessary to cause the disease. The mutated gene can be inherited from either parent or can be the result of a changed gene in the affected individual. The risk of passing the mutated gene from an affected parent to child is 50% for each pregnancy. The risk is the same for males and females.In most people with WSS, the change in the KMT2A gene that caused the disorder was not inherited from a parent but occurred spontaneously (de novo) in the individual with WSS. However, in a small number of patients reported in the medical literature, WSS was passed down from an affected parent to a child in an autosomal dominant manner.
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Affects of Wiedemann-Steiner Syndrome
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The estimated prevalence of WSS in the general population is approximately 1 in 1,000,000 live births. WSS has been diagnosed more often are in the United States, China, and countries in Europe. This is likely due to better availability of genetic testing in these countries.
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Affects of Wiedemann-Steiner Syndrome. The estimated prevalence of WSS in the general population is approximately 1 in 1,000,000 live births. WSS has been diagnosed more often are in the United States, China, and countries in Europe. This is likely due to better availability of genetic testing in these countries.
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Related disorders of Wiedemann-Steiner Syndrome
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Some features of Coffin-Siris syndrome, Kabuki syndrome, Cornelia de Lange syndrome, Rubinstein-Taybi syndrome, Noonan syndrome, and Suleiman-El-Hattab syndrome may be similar to those of Wiedemann-Steiner syndrome. These conditions are described below. Comparisons may be useful for a differential diagnosis. 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 changes may include an abnormally small head (microcephaly) or large head (macrocephaly), a wide and flat nose, a wide mouth with thick, prominent lips, thick eyebrows and eyelashes or excess hair growth in unusual places such as the back (hypertrichosis) and sparse scalp hair. In addition, affected infants and children may have short pinkies and toes with underdeveloped (hypoplastic) or absent nails, other differences 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. Changes in seven different genes, ARID1A, ARID1B, ARID2, SMARCA4, SMARCB1, SMARCE1 and SOX11 have been found to cause CSS. CSS can be inherited in an autosomal dominant pattern, but most cases appear to be the result of a new genetic change that is not inherited. (For more information on this disorder, choose “Coffin-Siris Syndrome” as your search term in the Rare Disease Database.)Kabuki syndrome is a rare genetic disorder that involves many organ systems and may be evident at birth (congenital). Individuals have certain facial features, including long eye openings (long palpebral fissures), arched, broad, and sparse eyebrows, large, prominent or cupped ears and a flat nose. Many patients will have delayed growth after birth, skeletal differences and some degree of intellectual disability. Other features include persistent fingertip pads, increased susceptibility to infections, autoimmune disorders, feeding problems, hormonal (endocrine) abnormalities, seizures, hearing loss, heart problems present at birth (congenital heart defects), cleft lip and/or palate and digestive system (gastrointestinal) differences. The presentation of the disease can vary between individuals. Most individuals with Kabuki syndrome have a change in the KMT2D gene, while fewer individuals will have a change in the KDM6A gene. The condition can be inherited in an autosomal dominant or X-linked manner. (For more information on this disorder, choose “Kabuki Syndrome” as your search term in the Rare Disease Database.) Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is generally apparent at birth (congenital). Associated symptoms and findings typically include delays in physical development before and after birth (prenatal and postnatal growth retardation), abnormalities of the head and facial (craniofacial) area, a distinctive facial appearance, differences of the hands and arms (upper limbs) and mild to severe intellectual disability. Many infants and children with the disorder have an unusually small, short head (microbrachycephaly), a prominent vertical groove between the upper lip and nose (philtrum), a flat nose, upturned nostrils (anteverted nares) and a small chin (micrognathia). Additional facial abnormalities may include thin, downturned lips, low-set ears, arched, well-defined eyebrows that grow together across the base of the nose (synophrys), an unusually low hairline on the forehead and the back of the neck and curly, unusually long eyelashes. Affected individuals may also have distinctive changes to the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of the fifth fingers and webbing (syndactyly) of certain toes. Less commonly, there may be absence of the forearms, hands and fingers. Infants with CdLS may also have feeding and breathing difficulties, an increased susceptibility to respiratory infections, a low-pitched “growling” cry and a low voice, heart problems, delayed skeletal maturation, hearing loss or other physical abnormalities. The range and severity of associated symptoms and findings may be extremely variable from person to person. CdLS can be inherited as an autosomal dominant condition or an X-linked condition. Seven genes have been found to be associated with CdLS including NIPBL, SMC1A, SMC3, Rad21, HDAC8, ANKRD11, and BRD4. Most affected individuals have a new genetic change that is not inherited from a parent. Other genes may be found to be associated with CdLS in the future. (For more information on this disorder, choose “Cornelia de Lange Syndrome” as your search term in the Rare Disease Database.) Rubinstein-Taybi is a rare genetic condition that can be apparent at birth (congenital). Patients with the condition have distinctive facial features, including downward slanting eyes (down slanted palpebral fissures), low-hanging nasal septum (columella), high roof of the mouth (palate), a grimacing smile and a rare dental anomaly called tallen cusps. In addition to facial features, the condition is characterized by the presence of intellectual disability to varying degrees, short stature, hand differences and growth delays after birth. Other features of the condition may include heart problems, kidney (renal) abnormalities, undescended testes (cryptorchidism), sight and hearing difficulties, respiratory difficulties, feeding problems, recurrent infections, and constipation. Patients may have genetic changes in the CREBBP gene or EP300 gene. Rubinstein-Taybi is inherited in an autosomal dominant manner, but most cases appear to be the result of a new genetic change that is not inherited. (For more information on this disorder, choose “Rubinstein-Taybi” as your search term in the Rare Disease Database.)Noonan syndrome is a genetic disorder that is typically evident at birth (congenital). The disorder is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. Many affected individuals have abnormalities that can include a distinctive facial appearance, a broad or webbed neck, a low posterior hairline, a typical chest deformity and short stature. Characteristic features of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism), skin folds that may cover the eyes’ inner corners (epicanthal folds), drooping of the upper eyelids (ptosis), a small jaw (micrognathia), a short nose with broad base and low-set, posteriorly rotated ears. Distinctive skeletal changes are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis) and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart problems. Additional abnormalities may include problems with the blood vessels or blood clotting, learning difficulties or mild intellectual disability, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males and/or other symptoms and findings. Noonan syndrome can be caused by changes in more than eight genes. Changes in PTNP11 are found in 50% of cases. Other genes that can cause Noonan syndrome include: SOS1, LZTR1, RAF1, RIT1, KRAS, BRAF, MAP2K1, MRAS, NRAS, RASA2, RRAS2 and SOS2. Most of the time, the condition is inherited in an autosomal dominant manner. Noonan syndrome caused by genetic changes in LZTR1 can be inherited in either an autosomal dominant or an autosomal recessive manner. (For more information on this disorder, choose “Noonan Syndrome” as your search term in the Rare Disease Database.) Suleiman-El-Hattab syndrome is an autosomal recessive genetic disorder that may be evident at birth (congenital). It is characterized by distinct facial features, hypotonia, feeding difficulties, developmental delay, intellectual disability and a generally happy demeanor. Features of the head and facial (craniofacial) area may include a small head (microcephaly), thick arched eyebrows that grow together at the base of the nose (synophrys), increased distance between the eyes (hypertelorism), skin folds that may cover the eyes' inner corners (epicanthal folds), low-set ears, wide nose (broad nasal bridge) and a thin upper lip. Additional, more variable features may include recurrent infections, heart problems, undescended testes (cryptorchidism), seizures and hand and feet differences. Suleiman-El-Hattab syndrome is caused by changes in the TASP1 gene.
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Related disorders of Wiedemann-Steiner Syndrome. Some features of Coffin-Siris syndrome, Kabuki syndrome, Cornelia de Lange syndrome, Rubinstein-Taybi syndrome, Noonan syndrome, and Suleiman-El-Hattab syndrome may be similar to those of Wiedemann-Steiner syndrome. These conditions are described below. Comparisons may be useful for a differential diagnosis. 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 changes may include an abnormally small head (microcephaly) or large head (macrocephaly), a wide and flat nose, a wide mouth with thick, prominent lips, thick eyebrows and eyelashes or excess hair growth in unusual places such as the back (hypertrichosis) and sparse scalp hair. In addition, affected infants and children may have short pinkies and toes with underdeveloped (hypoplastic) or absent nails, other differences 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. Changes in seven different genes, ARID1A, ARID1B, ARID2, SMARCA4, SMARCB1, SMARCE1 and SOX11 have been found to cause CSS. CSS can be inherited in an autosomal dominant pattern, but most cases appear to be the result of a new genetic change that is not inherited. (For more information on this disorder, choose “Coffin-Siris Syndrome” as your search term in the Rare Disease Database.)Kabuki syndrome is a rare genetic disorder that involves many organ systems and may be evident at birth (congenital). Individuals have certain facial features, including long eye openings (long palpebral fissures), arched, broad, and sparse eyebrows, large, prominent or cupped ears and a flat nose. Many patients will have delayed growth after birth, skeletal differences and some degree of intellectual disability. Other features include persistent fingertip pads, increased susceptibility to infections, autoimmune disorders, feeding problems, hormonal (endocrine) abnormalities, seizures, hearing loss, heart problems present at birth (congenital heart defects), cleft lip and/or palate and digestive system (gastrointestinal) differences. The presentation of the disease can vary between individuals. Most individuals with Kabuki syndrome have a change in the KMT2D gene, while fewer individuals will have a change in the KDM6A gene. The condition can be inherited in an autosomal dominant or X-linked manner. (For more information on this disorder, choose “Kabuki Syndrome” as your search term in the Rare Disease Database.) Cornelia de Lange syndrome (CdLS) is a rare genetic disorder that is generally apparent at birth (congenital). Associated symptoms and findings typically include delays in physical development before and after birth (prenatal and postnatal growth retardation), abnormalities of the head and facial (craniofacial) area, a distinctive facial appearance, differences of the hands and arms (upper limbs) and mild to severe intellectual disability. Many infants and children with the disorder have an unusually small, short head (microbrachycephaly), a prominent vertical groove between the upper lip and nose (philtrum), a flat nose, upturned nostrils (anteverted nares) and a small chin (micrognathia). Additional facial abnormalities may include thin, downturned lips, low-set ears, arched, well-defined eyebrows that grow together across the base of the nose (synophrys), an unusually low hairline on the forehead and the back of the neck and curly, unusually long eyelashes. Affected individuals may also have distinctive changes to the limbs, such as unusually small hands and feet, inward deviation (clinodactyly) of the fifth fingers and webbing (syndactyly) of certain toes. Less commonly, there may be absence of the forearms, hands and fingers. Infants with CdLS may also have feeding and breathing difficulties, an increased susceptibility to respiratory infections, a low-pitched “growling” cry and a low voice, heart problems, delayed skeletal maturation, hearing loss or other physical abnormalities. The range and severity of associated symptoms and findings may be extremely variable from person to person. CdLS can be inherited as an autosomal dominant condition or an X-linked condition. Seven genes have been found to be associated with CdLS including NIPBL, SMC1A, SMC3, Rad21, HDAC8, ANKRD11, and BRD4. Most affected individuals have a new genetic change that is not inherited from a parent. Other genes may be found to be associated with CdLS in the future. (For more information on this disorder, choose “Cornelia de Lange Syndrome” as your search term in the Rare Disease Database.) Rubinstein-Taybi is a rare genetic condition that can be apparent at birth (congenital). Patients with the condition have distinctive facial features, including downward slanting eyes (down slanted palpebral fissures), low-hanging nasal septum (columella), high roof of the mouth (palate), a grimacing smile and a rare dental anomaly called tallen cusps. In addition to facial features, the condition is characterized by the presence of intellectual disability to varying degrees, short stature, hand differences and growth delays after birth. Other features of the condition may include heart problems, kidney (renal) abnormalities, undescended testes (cryptorchidism), sight and hearing difficulties, respiratory difficulties, feeding problems, recurrent infections, and constipation. Patients may have genetic changes in the CREBBP gene or EP300 gene. Rubinstein-Taybi is inherited in an autosomal dominant manner, but most cases appear to be the result of a new genetic change that is not inherited. (For more information on this disorder, choose “Rubinstein-Taybi” as your search term in the Rare Disease Database.)Noonan syndrome is a genetic disorder that is typically evident at birth (congenital). The disorder is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. Many affected individuals have abnormalities that can include a distinctive facial appearance, a broad or webbed neck, a low posterior hairline, a typical chest deformity and short stature. Characteristic features of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism), skin folds that may cover the eyes’ inner corners (epicanthal folds), drooping of the upper eyelids (ptosis), a small jaw (micrognathia), a short nose with broad base and low-set, posteriorly rotated ears. Distinctive skeletal changes are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis) and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart problems. Additional abnormalities may include problems with the blood vessels or blood clotting, learning difficulties or mild intellectual disability, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males and/or other symptoms and findings. Noonan syndrome can be caused by changes in more than eight genes. Changes in PTNP11 are found in 50% of cases. Other genes that can cause Noonan syndrome include: SOS1, LZTR1, RAF1, RIT1, KRAS, BRAF, MAP2K1, MRAS, NRAS, RASA2, RRAS2 and SOS2. Most of the time, the condition is inherited in an autosomal dominant manner. Noonan syndrome caused by genetic changes in LZTR1 can be inherited in either an autosomal dominant or an autosomal recessive manner. (For more information on this disorder, choose “Noonan Syndrome” as your search term in the Rare Disease Database.) Suleiman-El-Hattab syndrome is an autosomal recessive genetic disorder that may be evident at birth (congenital). It is characterized by distinct facial features, hypotonia, feeding difficulties, developmental delay, intellectual disability and a generally happy demeanor. Features of the head and facial (craniofacial) area may include a small head (microcephaly), thick arched eyebrows that grow together at the base of the nose (synophrys), increased distance between the eyes (hypertelorism), skin folds that may cover the eyes' inner corners (epicanthal folds), low-set ears, wide nose (broad nasal bridge) and a thin upper lip. Additional, more variable features may include recurrent infections, heart problems, undescended testes (cryptorchidism), seizures and hand and feet differences. Suleiman-El-Hattab syndrome is caused by changes in the TASP1 gene.
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Diagnosis of Wiedemann-Steiner Syndrome
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Wiedemann-Steiner syndrome may be suspected in a child with certain facial features, developmental delay, intellectual disability and excessive body hair. Patients may or may not have organ problems. There are currently no established clinical diagnostic criteria for Wiedemann-Steiner syndrome. Therefore, a diagnosis cannot be established by clinical features alone. Genetic testing for pathogenic variants in the KMT2A gene is required to confirm the diagnosis. A single gene test or a test on a group of genes (panel) may be recommended, depending on the patient’s symptoms. Almost all pathogenic variants can be detected using a technology called next-generation sequencing. If next-generation sequencing does not identify a relevant genetic change, analysis of missing or extra pieces of chromosomes (deletions and duplication analysis) may be performed. Sometimes, a genetic test result will show a variant in the KMT2A gene that may or may not be related to the disease (variant of uncertain significance). When this is the case, another test may be recommended to evaluate how the KMT2A gene is working in the patient to help make a diagnosis. Clinical Testing and Work-Up
The clinical work-up and testing for Wiedemann-Steiner syndrome should be tailored to each patient's individual needs and medical history.Endocrine evaluations including blood tests and X-rays may be done to help detect hormone deficiencies and differences in bone growth.Neurological evaluations, including magnetic resonance imaging (MRI), are important for detecting structural brain abnormalities like abnormal corpus callosum or abnormal myelination, which are present in about half of affected individuals. An electroencephalogram (EEG) should be performed if seizures are a concern, which occur in about 1 in 5 affected individuals. Patients with KMT2A genetic changes require close monitoring of developmental milestones. A developmental assessment can identify any developmental delays or intellectual disabilities, which are usually mild to moderate. Assessments of speech/language, cognitive function, and motor function are helpful for early intervention and special education.A neuropsychiatric evaluation should be conducted later in childhood as behavioral problems, including autism, attention deficit and hyperactivity and aggressive behavior, are common. Orthopedic, occupational therapy and physical therapy evaluations should be performed to assess gross and fine motor skills, as well as any signs or symptoms suggestive of vertebral anomalies and hip dysplasia. Gastroenterology and nutrition evaluations are important as infants and children can have feeding problems and poor weight gain, requiring tube feeding. Assessments for constipation or bowel dysfunction should be conducted.Cardiovascular evaluations, including echocardiograms and electrocardiogram, are necessary to detect congenital cardiac abnormalities (usually minor, such as persistent ductus arteriosus and arrhythmia). Immunologic evaluations can identify an immune deficiency, which has been detected in some patients by monitoring for signs of frequent infection, abnormal immunoglobulin levels and insufficient response to pneumococcal vaccinations. Patients with Wiedemann-Steiner syndrome may also experience ear, nose, and throat issues, including sleep apnea and hearing loss, which should be assessed and treated accordingly by an otolaryngologist. In addition, a comprehensive eye exam should be conducted by an ophthalmologist since eye abnormalities such as strabismus (crossed eye), astigmatism (imperfection in the curvature of the eye's cornea or lens) and blepharoptosis (drooping of upper eyelid) are common. Patients with Wiedemann-Steiner syndrome may also benefit from immunology evaluations to assess immunoglobulins, response to vaccines and recurrent infections (if applicable). In addition, gastrointestinal evaluation, through abdominal ultrasounds and monitoring of growth and feeding difficulties, may be warranted.
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Diagnosis of Wiedemann-Steiner Syndrome. Wiedemann-Steiner syndrome may be suspected in a child with certain facial features, developmental delay, intellectual disability and excessive body hair. Patients may or may not have organ problems. There are currently no established clinical diagnostic criteria for Wiedemann-Steiner syndrome. Therefore, a diagnosis cannot be established by clinical features alone. Genetic testing for pathogenic variants in the KMT2A gene is required to confirm the diagnosis. A single gene test or a test on a group of genes (panel) may be recommended, depending on the patient’s symptoms. Almost all pathogenic variants can be detected using a technology called next-generation sequencing. If next-generation sequencing does not identify a relevant genetic change, analysis of missing or extra pieces of chromosomes (deletions and duplication analysis) may be performed. Sometimes, a genetic test result will show a variant in the KMT2A gene that may or may not be related to the disease (variant of uncertain significance). When this is the case, another test may be recommended to evaluate how the KMT2A gene is working in the patient to help make a diagnosis. Clinical Testing and Work-Up
The clinical work-up and testing for Wiedemann-Steiner syndrome should be tailored to each patient's individual needs and medical history.Endocrine evaluations including blood tests and X-rays may be done to help detect hormone deficiencies and differences in bone growth.Neurological evaluations, including magnetic resonance imaging (MRI), are important for detecting structural brain abnormalities like abnormal corpus callosum or abnormal myelination, which are present in about half of affected individuals. An electroencephalogram (EEG) should be performed if seizures are a concern, which occur in about 1 in 5 affected individuals. Patients with KMT2A genetic changes require close monitoring of developmental milestones. A developmental assessment can identify any developmental delays or intellectual disabilities, which are usually mild to moderate. Assessments of speech/language, cognitive function, and motor function are helpful for early intervention and special education.A neuropsychiatric evaluation should be conducted later in childhood as behavioral problems, including autism, attention deficit and hyperactivity and aggressive behavior, are common. Orthopedic, occupational therapy and physical therapy evaluations should be performed to assess gross and fine motor skills, as well as any signs or symptoms suggestive of vertebral anomalies and hip dysplasia. Gastroenterology and nutrition evaluations are important as infants and children can have feeding problems and poor weight gain, requiring tube feeding. Assessments for constipation or bowel dysfunction should be conducted.Cardiovascular evaluations, including echocardiograms and electrocardiogram, are necessary to detect congenital cardiac abnormalities (usually minor, such as persistent ductus arteriosus and arrhythmia). Immunologic evaluations can identify an immune deficiency, which has been detected in some patients by monitoring for signs of frequent infection, abnormal immunoglobulin levels and insufficient response to pneumococcal vaccinations. Patients with Wiedemann-Steiner syndrome may also experience ear, nose, and throat issues, including sleep apnea and hearing loss, which should be assessed and treated accordingly by an otolaryngologist. In addition, a comprehensive eye exam should be conducted by an ophthalmologist since eye abnormalities such as strabismus (crossed eye), astigmatism (imperfection in the curvature of the eye's cornea or lens) and blepharoptosis (drooping of upper eyelid) are common. Patients with Wiedemann-Steiner syndrome may also benefit from immunology evaluations to assess immunoglobulins, response to vaccines and recurrent infections (if applicable). In addition, gastrointestinal evaluation, through abdominal ultrasounds and monitoring of growth and feeding difficulties, may be warranted.
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Therapies of Wiedemann-Steiner Syndrome
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Patients with WSS are treated for the specific symptoms they have. May different medical specialists may be involved in their care. Treatment for feeding difficulty may include feeding therapy and nasogastric or gastrostomy tube placement.Seizures are treated with standard anti-seizure medications. Constipation or bowel dysfunction is treated with laxatives or stool softeners. Endocrine abnormalities, including growth hormone deficiency and thyroid dysfunction, may require hormone replacement therapy. Obstructive sleep apnea may require the use of a continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) machine or surgical removal of tonsils and adenoids. Immune deficiency may be managed with intravenous immunoglobulin (IVIG) in those with low antibody levels and prophylactic antibiotics in those with frequent infections.Heart abnormalities may require medication or surgery.Other problems are treated by relevant specialists. Patients with global developmental delay or intellectual disability may require special education and appropriate assessments at school. Physical therapy, occupational therapy, speech therapy and early intervention can help improve physical and cognitive development, quality of life and independence in daily activities.Patients with global developmental delay or intellectual disability may require special education and appropriate assessments at school. Genetic counseling is recommended for families with an affected child.
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Therapies of Wiedemann-Steiner Syndrome. Patients with WSS are treated for the specific symptoms they have. May different medical specialists may be involved in their care. Treatment for feeding difficulty may include feeding therapy and nasogastric or gastrostomy tube placement.Seizures are treated with standard anti-seizure medications. Constipation or bowel dysfunction is treated with laxatives or stool softeners. Endocrine abnormalities, including growth hormone deficiency and thyroid dysfunction, may require hormone replacement therapy. Obstructive sleep apnea may require the use of a continuous positive airway pressure (CPAP) or bilevel positive airway pressure (BiPAP) machine or surgical removal of tonsils and adenoids. Immune deficiency may be managed with intravenous immunoglobulin (IVIG) in those with low antibody levels and prophylactic antibiotics in those with frequent infections.Heart abnormalities may require medication or surgery.Other problems are treated by relevant specialists. Patients with global developmental delay or intellectual disability may require special education and appropriate assessments at school. Physical therapy, occupational therapy, speech therapy and early intervention can help improve physical and cognitive development, quality of life and independence in daily activities.Patients with global developmental delay or intellectual disability may require special education and appropriate assessments at school. Genetic counseling is recommended for families with an affected child.
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Overview of Wildervanck Syndrome
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Wildervanck syndrome, also known as cervicooculoacoustic syndrome, is a rare genetic disorder that primarily affects females. The disorder is characterized by a skeletal condition known as Klippel-Feil syndrome (KFS); abnormalities of certain eye (ocular) movements (i.e., Duane syndrome); and/or hearing impairment that is present at birth (congenital). In individuals with KFS, there is abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Duane syndrome is characterized by limitation or absence of certain horizontal eye movements; retraction or “drawing back” of the eyeball into the eye cavity (orbit) upon attempting to look inward; and, in some cases, abnormal deviation of one eye in relation to the other (strabismus). In some affected individuals, additional physical abnormalities may also be present. In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically).
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Overview of Wildervanck Syndrome. Wildervanck syndrome, also known as cervicooculoacoustic syndrome, is a rare genetic disorder that primarily affects females. The disorder is characterized by a skeletal condition known as Klippel-Feil syndrome (KFS); abnormalities of certain eye (ocular) movements (i.e., Duane syndrome); and/or hearing impairment that is present at birth (congenital). In individuals with KFS, there is abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Duane syndrome is characterized by limitation or absence of certain horizontal eye movements; retraction or “drawing back” of the eyeball into the eye cavity (orbit) upon attempting to look inward; and, in some cases, abnormal deviation of one eye in relation to the other (strabismus). In some affected individuals, additional physical abnormalities may also be present. In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically).
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Symptoms of Wildervanck Syndrome
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Wildervanck syndrome is typically characterized by three primary findings (triad). These include abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (Klippel-Feil syndrome); impairment or absence of certain eye (ocular) movements (Duane syndrome); and hearing impairment that is present at birth. However, according to some reports, this triad may be incomplete in some individuals with Wildervanck syndrome. In addition, in some cases, additional physical findings or intellectual disability may be present.Researchers have described three major subtypes of Klippel-Feil syndrome (KFS). According to this classification, KFS type I is characterized by extensive fusion of vertebrae of the neck (cervical vertebrae) and the upper back (i.e., upper thoracic vertebrae). In KFS type II, there is localized union or fusion at one or two cervical or thoracic vertebrae associated with incomplete development of one half of certain vertebrae (hemivertebrae) or other malformations of cervical vertebrae. KFS type III is characterized by fusion of vertebrae of the neck as well as vertebrae of the upper or lower back (i.e., lower thoracic or lumbar vertebrae).Individuals with Wildervanck syndrome who are affected by KFS also tend to have an unusually short neck. In severe cases, the head may appear to be situated directly on the trunk. KFS may also be associated with limited movements of the head and neck and a low hairline at the back of the head (posterior hairline) that may extend to the shoulders. In addition, the face often appears dissimilar from one side to the other (facial asymmetry), and the neck may be abnormally twisted (torticollis), with the head rotated into an abnormal position. Some individuals with KFS may have a risk of developing neurological complications due to instability of cervical vertebrae and associated spinal cord injury that may occur spontaneously or following minor trauma. Such complications may include associated pain; unusual sensations (paresthesia), such as tingling or prickling; increased reflex reactions (hyperreflexia), weakness or paralysis of one side of the body (hemiplegia) or of the legs and the lower part of the body (paraplegia), or other findings. According to some researchers, evidence suggests that Wildervanck syndrome may be a clinical variant of KFS. (For further information on KFS, please see the “Related Disorders” section of this report below.)In some instances, Wildervanck syndrome may also be characterized by additional skeletal abnormalities. These may include incomplete development of certain vertebrae, leaving a portion of the spinal cord exposed (spina bifida); abnormal curvature of the spine (scoliosis), rib defects; and/or a condition known as Sprengel’s deformity. This condition is characterized by elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the shoulder blade. There are some patients that only have an abnormal curvature of the spine (scoliosis).As mentioned above, Wildervanck syndrome is also associated with Duane syndrome, a condition characterized by limitation or absence of certain horizontal eye movements and other eye (ocular) abnormalities. In those with Duane syndrome, there may be an impaired or absent ability to move the eyes outward (abduction), inward (adduction), or both. In addition, upon attempting to look inward, there may be abnormal narrowing of the eye slit (palpebral fissure narrowing) and retraction or “drawing back” of the eyeball into the eye cavity (orbit). Such abnormalities may affect one or both eyes (unilateral or bilateral). In some cases, affected individuals may also have abnormal inward or outward deviation of one eye in relation to the other (convergent or divergent strabismus).In some individuals with Wildervanck syndrome, additional ocular abnormalities may be present. For example, some affected individuals may have pseudopapilledema, a condition in which swelling of the optic disc may be present from birth for unknown reasons. The optic disc, also known as the “blind spot,” is the portion of the optic nerve that joins with the nerve-rich innermost region of the eye (retina). Additional ocular abnormalities may include incomplete or partial dislocation of the lenses of both eyes (bilateral subluxation), the formation of cysts on the eyeballs (epibulbar dermoids and lipodermoids) and drooping of the upper eyelids causing a narrowing of the palpebral aperture (blepharoptosis).Wildervanck syndrome is also typically associated with hearing impairment at birth (congenital). Such hearing loss may result from impaired transmission of sound from the outer or middle ear to the inner ear (conductive hearing loss); failed transmission of sound impulses from the inner ear to the brain (sensorineural hearing loss); or both (mixed hearing loss). One or both ears may be affected (unilateral or bilateral hearing impairment). According to some reports, most affected individuals have sensorineural hearing loss due to structural abnormalities of the inner ear. For example, there may be abnormalities of the coiled bony passage (cochlea) that transforms sound vibrations into nerve impulses for transmission to the brain. Additional defects may include underdevelopment or malformation of regions involved with the sensation of position, movement, and balance (vestibular apparatus); absence of the nerve that conveys impulses for the sensation of sound and balance to the brain (vestibulocochlear nerve); and/or other abnormalities.Some individuals with Wildervanck syndrome may also have additional abnormalities. For example, some may have malformations of the head and facial (craniofacial) area, such as an abnormally small head (microcephaly) or incomplete closure of the roof of the mouth (cleft palate). In addition, in some cases, Wildervanck syndrome may be associated with hydrocephalus, a condition in which there is obstructed flow or impaired absorption of the fluid surrounding the brain and spinal cord (cerebrospinal fluid [CSF]), resulting in increasing fluid pressure in the brain. Rarely, in some affected infants, there may be protrusion of the membranes surrounding the brain (meninges) through a defect in the back of the skull (occipital meningocele). Additional physical features may include abnormal outgrowths of skin (skin tags) or pits in front of the ears (preauricular tags and pits); kidney (renal) defects; the presence of lumps of solid matter (gallstones) within the gallbladder (cholelithiasis).Some patients with structural malformations of the heart have been reported, (congenital heart [cardiac] defects). Cardiac defects may include an abnormal opening in the fibrous partition (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects) and little holes in the heart valves (aortic valve fenestration). Recently, some patients were reported with dilatation of the arteries from the heart (aneurism of the coronary artery) or rupture of the arteries of the spine (vertebral artery dissection). There are also some patients with associated vascular malformations such as only one artery of the heart (single coronary artery) or the persistence of a vena in the thorax that should disappear before birth (persistent left superior vena cava).In addition, although intelligence is usually normal, intellectual disability has been reported in some affected individuals. Short stature has also been seen in some patients, and one individual was diagnosed with idiopathic growth hormone deficiency.
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Symptoms of Wildervanck Syndrome. Wildervanck syndrome is typically characterized by three primary findings (triad). These include abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (Klippel-Feil syndrome); impairment or absence of certain eye (ocular) movements (Duane syndrome); and hearing impairment that is present at birth. However, according to some reports, this triad may be incomplete in some individuals with Wildervanck syndrome. In addition, in some cases, additional physical findings or intellectual disability may be present.Researchers have described three major subtypes of Klippel-Feil syndrome (KFS). According to this classification, KFS type I is characterized by extensive fusion of vertebrae of the neck (cervical vertebrae) and the upper back (i.e., upper thoracic vertebrae). In KFS type II, there is localized union or fusion at one or two cervical or thoracic vertebrae associated with incomplete development of one half of certain vertebrae (hemivertebrae) or other malformations of cervical vertebrae. KFS type III is characterized by fusion of vertebrae of the neck as well as vertebrae of the upper or lower back (i.e., lower thoracic or lumbar vertebrae).Individuals with Wildervanck syndrome who are affected by KFS also tend to have an unusually short neck. In severe cases, the head may appear to be situated directly on the trunk. KFS may also be associated with limited movements of the head and neck and a low hairline at the back of the head (posterior hairline) that may extend to the shoulders. In addition, the face often appears dissimilar from one side to the other (facial asymmetry), and the neck may be abnormally twisted (torticollis), with the head rotated into an abnormal position. Some individuals with KFS may have a risk of developing neurological complications due to instability of cervical vertebrae and associated spinal cord injury that may occur spontaneously or following minor trauma. Such complications may include associated pain; unusual sensations (paresthesia), such as tingling or prickling; increased reflex reactions (hyperreflexia), weakness or paralysis of one side of the body (hemiplegia) or of the legs and the lower part of the body (paraplegia), or other findings. According to some researchers, evidence suggests that Wildervanck syndrome may be a clinical variant of KFS. (For further information on KFS, please see the “Related Disorders” section of this report below.)In some instances, Wildervanck syndrome may also be characterized by additional skeletal abnormalities. These may include incomplete development of certain vertebrae, leaving a portion of the spinal cord exposed (spina bifida); abnormal curvature of the spine (scoliosis), rib defects; and/or a condition known as Sprengel’s deformity. This condition is characterized by elevation and/or underdevelopment of the shoulder blade (scapula), limited movement of the arm on the affected side, and the development of a lump at the base of the neck due to elevation of the shoulder blade. There are some patients that only have an abnormal curvature of the spine (scoliosis).As mentioned above, Wildervanck syndrome is also associated with Duane syndrome, a condition characterized by limitation or absence of certain horizontal eye movements and other eye (ocular) abnormalities. In those with Duane syndrome, there may be an impaired or absent ability to move the eyes outward (abduction), inward (adduction), or both. In addition, upon attempting to look inward, there may be abnormal narrowing of the eye slit (palpebral fissure narrowing) and retraction or “drawing back” of the eyeball into the eye cavity (orbit). Such abnormalities may affect one or both eyes (unilateral or bilateral). In some cases, affected individuals may also have abnormal inward or outward deviation of one eye in relation to the other (convergent or divergent strabismus).In some individuals with Wildervanck syndrome, additional ocular abnormalities may be present. For example, some affected individuals may have pseudopapilledema, a condition in which swelling of the optic disc may be present from birth for unknown reasons. The optic disc, also known as the “blind spot,” is the portion of the optic nerve that joins with the nerve-rich innermost region of the eye (retina). Additional ocular abnormalities may include incomplete or partial dislocation of the lenses of both eyes (bilateral subluxation), the formation of cysts on the eyeballs (epibulbar dermoids and lipodermoids) and drooping of the upper eyelids causing a narrowing of the palpebral aperture (blepharoptosis).Wildervanck syndrome is also typically associated with hearing impairment at birth (congenital). Such hearing loss may result from impaired transmission of sound from the outer or middle ear to the inner ear (conductive hearing loss); failed transmission of sound impulses from the inner ear to the brain (sensorineural hearing loss); or both (mixed hearing loss). One or both ears may be affected (unilateral or bilateral hearing impairment). According to some reports, most affected individuals have sensorineural hearing loss due to structural abnormalities of the inner ear. For example, there may be abnormalities of the coiled bony passage (cochlea) that transforms sound vibrations into nerve impulses for transmission to the brain. Additional defects may include underdevelopment or malformation of regions involved with the sensation of position, movement, and balance (vestibular apparatus); absence of the nerve that conveys impulses for the sensation of sound and balance to the brain (vestibulocochlear nerve); and/or other abnormalities.Some individuals with Wildervanck syndrome may also have additional abnormalities. For example, some may have malformations of the head and facial (craniofacial) area, such as an abnormally small head (microcephaly) or incomplete closure of the roof of the mouth (cleft palate). In addition, in some cases, Wildervanck syndrome may be associated with hydrocephalus, a condition in which there is obstructed flow or impaired absorption of the fluid surrounding the brain and spinal cord (cerebrospinal fluid [CSF]), resulting in increasing fluid pressure in the brain. Rarely, in some affected infants, there may be protrusion of the membranes surrounding the brain (meninges) through a defect in the back of the skull (occipital meningocele). Additional physical features may include abnormal outgrowths of skin (skin tags) or pits in front of the ears (preauricular tags and pits); kidney (renal) defects; the presence of lumps of solid matter (gallstones) within the gallbladder (cholelithiasis).Some patients with structural malformations of the heart have been reported, (congenital heart [cardiac] defects). Cardiac defects may include an abnormal opening in the fibrous partition (septum) that separates the upper or lower chambers of the heart (atrial or ventricular septal defects) and little holes in the heart valves (aortic valve fenestration). Recently, some patients were reported with dilatation of the arteries from the heart (aneurism of the coronary artery) or rupture of the arteries of the spine (vertebral artery dissection). There are also some patients with associated vascular malformations such as only one artery of the heart (single coronary artery) or the persistence of a vena in the thorax that should disappear before birth (persistent left superior vena cava).In addition, although intelligence is usually normal, intellectual disability has been reported in some affected individuals. Short stature has also been seen in some patients, and one individual was diagnosed with idiopathic growth hormone deficiency.
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Causes of Wildervanck Syndrome
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In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically). Because the disorder primarily affects females, some researchers suggest that Wildervanck syndrome may be transmitted as an X-linked dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.X-linked disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, whereas males have one X chromosome and one Y chromosome. In females, certain disease traits on the X chromosome may in some cases be “masked” by the normal gene on the other X chromosome (X-chromosome inactivation). However, since males have only one X chromosome, if they inherit a gene for a disease present on the X, it is more likely to be fully expressed. According to researchers, in males who inherit a disease gene for an X-linked dominant disorder (hemizygotes), it is suspected that full expression of the disorder may be associated with a more severe course that may be incompatible with life even before birth.One group of researchers found a small deletion of chromosome X which they believe could explain Wildervanck syndrome in one patient.According to other researchers, Wildervanck syndrome may result from the interaction of several different genes (polygenic inheritance), possibly in combination with certain environmental factors (multifactorial inheritance), with limitation to females.
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Causes of Wildervanck Syndrome. In most cases, Wildervanck syndrome appears to occur randomly for unknown reasons (sporadically). Because the disorder primarily affects females, some researchers suggest that Wildervanck syndrome may be transmitted as an X-linked dominant trait. Human traits, including the classic genetic diseases, are the product of the interaction of two genes, one received from the father and one from the mother.X-linked disorders are conditions that are coded on the X chromosome. Females have two X chromosomes, whereas males have one X chromosome and one Y chromosome. In females, certain disease traits on the X chromosome may in some cases be “masked” by the normal gene on the other X chromosome (X-chromosome inactivation). However, since males have only one X chromosome, if they inherit a gene for a disease present on the X, it is more likely to be fully expressed. According to researchers, in males who inherit a disease gene for an X-linked dominant disorder (hemizygotes), it is suspected that full expression of the disorder may be associated with a more severe course that may be incompatible with life even before birth.One group of researchers found a small deletion of chromosome X which they believe could explain Wildervanck syndrome in one patient.According to other researchers, Wildervanck syndrome may result from the interaction of several different genes (polygenic inheritance), possibly in combination with certain environmental factors (multifactorial inheritance), with limitation to females.
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Affects of Wildervanck Syndrome
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As mentioned above, Wildervanck syndrome primarily affects females. Since the disorder was originally described in 1952 (L.S. Wildervanck), almost 90 cases have been reported in the medical literature. According to some reports, approximately one percent of females with hearing impairment may be affected by Wildervanck syndrome.
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Affects of Wildervanck Syndrome. As mentioned above, Wildervanck syndrome primarily affects females. Since the disorder was originally described in 1952 (L.S. Wildervanck), almost 90 cases have been reported in the medical literature. According to some reports, approximately one percent of females with hearing impairment may be affected by Wildervanck syndrome.
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Related disorders of Wildervanck Syndrome
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Symptoms of the following disorders may be similar to those of Wildervanck syndrome. Comparisons may be useful for a differential diagnosis:Duane syndrome is an eye movement disorder present at birth characterized by horizontal eye movement limitation [a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction), or in both directions]. In addition, when the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) and the eye opening (palpebral fissure) narrows. In some cases, when the eye attempts to look inward, it moves upward (upshoot) or downward (downshoot).Duane syndrome falls under the larger heading of strabismus (misalignment of the eyes) under the subclassification of incomitant strabismus (misalignment of the eyes that varies with gaze directions) and subheading of what was previously termed extraocular fibrosis syndromes (conditions associated with fibrosis of the muscles that move the eyes), now termed congenital cranial dysinnervation disorders (CCDDs). The CCDDs are a group of congenital neuromuscular diseases resulting from developmental errors in innervation; the abnormalities involve one or more cranial nerves/nuclei with absence of normal innervation and/or secondary aberrant innervation. Duane syndrome has been subdivided clinically into three types: Type 1, Type 2, and Type 3. (For further information, choose “Duane” as your search term in the Rare Disease Database.)Klippel-Feil syndrome (KFS) is a rare skeletal disorder primarily characterized by abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Some affected individuals may also have an abnormally short neck, restricted movement of the head and neck, and a low hairline at the back of the head (posterior hairline). The disorder is present at birth (congenital), but mild cases may go undiagnosed until later during life when symptoms worsen or first become apparent.In some individuals, KFS can be associated with a variety of additional symptoms and physical abnormalities. These may include abnormal curvature of the spine (scoliosis) and/or vertebral instability, spina bifida occulta, raised scapula (Sprengel’s deformity), absent rib(s) and other rib defects including cervical ribs, other skeletal abnormalities including skeletal malformations of the ear, nose, mouth and larynx including hearing impairment and cleft palate, malformations of the head and facial (craniofacial) area; anomalies of the urinary tract and/or kidney including absent or horse-shoe kidney; or structural abnormalities of the heart (congenital heart defects), mirror movements, webbing of the digits and digital hypoplasia. In addition, in some cases, neurological complications may result due to associated spinal cord injury.KFS may occur as an isolated abnormality or in association with certain syndromes. In many individuals with KFS, the condition appears to occur randomly for unknown reasons (sporadically). In other cases, KFS may be inherited as an autosomal dominant or autosomal recessive trait. Researchers have determined that some cases of KFS are associated with mutations of the GDF6, GDF3, MEOX1 or MYO18B genes. (For further information, please choose “Klippel Feil” as your search term in the Rare Disease Database.)Oculo-auriculo-vertebral spectrum (OAVS) refers to three rare disorders that many clinicians believe to be intimately related to one another and which represent the range of severity of the same disorder. These disorders are apparent at birth (congenital). As the name suggests, they involve malformations of the eyes, ears and spine.Oculo-auriculo-vertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome presents frequently as the most severe form. Hemifacial microstomia appears to be an intermediate form.The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. However, such abnormalities tend to involve the cheekbones, jaw, mouth, ears, eyes, and/or bones of the spinal column (vertebrae). Although, in most cases (about 60%), such malformations affect one side of the body (unilateral), approximately 10 to 33 percent of affected individuals have such malformations on both sides of the body (bilateral), with one side typically more affected than the other (asymmetry). In the majority of such cases, the right side is more severely affected than the left.In most cases OAVS appears to occur randomly, with no apparent cause (sporadic). However, in some cases, family histories suggest autosomal dominant or recessive inheritance. In addition, some researchers suggest that the disorder may be caused by the interaction of many genes, possibly in combination with environmental factors (multifactorial inheritance). (For further information on this disorder, choose “OAVS” as your search term in the Rare Disease Database.)There are additional disorders that may be characterized by skeletal, ocular, auditory, or other abnormalities similar to those potentially associated with Wildervanck syndrome. (For more information on such disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Related disorders of Wildervanck Syndrome. Symptoms of the following disorders may be similar to those of Wildervanck syndrome. Comparisons may be useful for a differential diagnosis:Duane syndrome is an eye movement disorder present at birth characterized by horizontal eye movement limitation [a limited ability to move the eye inward toward the nose (adduction), outward toward the ear (abduction), or in both directions]. In addition, when the affected eye(s) moves inward toward the nose, the eyeball retracts (pulls in) and the eye opening (palpebral fissure) narrows. In some cases, when the eye attempts to look inward, it moves upward (upshoot) or downward (downshoot).Duane syndrome falls under the larger heading of strabismus (misalignment of the eyes) under the subclassification of incomitant strabismus (misalignment of the eyes that varies with gaze directions) and subheading of what was previously termed extraocular fibrosis syndromes (conditions associated with fibrosis of the muscles that move the eyes), now termed congenital cranial dysinnervation disorders (CCDDs). The CCDDs are a group of congenital neuromuscular diseases resulting from developmental errors in innervation; the abnormalities involve one or more cranial nerves/nuclei with absence of normal innervation and/or secondary aberrant innervation. Duane syndrome has been subdivided clinically into three types: Type 1, Type 2, and Type 3. (For further information, choose “Duane” as your search term in the Rare Disease Database.)Klippel-Feil syndrome (KFS) is a rare skeletal disorder primarily characterized by abnormal union or fusion of two or more bones of the spinal column (vertebrae) within the neck (cervical vertebrae). Some affected individuals may also have an abnormally short neck, restricted movement of the head and neck, and a low hairline at the back of the head (posterior hairline). The disorder is present at birth (congenital), but mild cases may go undiagnosed until later during life when symptoms worsen or first become apparent.In some individuals, KFS can be associated with a variety of additional symptoms and physical abnormalities. These may include abnormal curvature of the spine (scoliosis) and/or vertebral instability, spina bifida occulta, raised scapula (Sprengel’s deformity), absent rib(s) and other rib defects including cervical ribs, other skeletal abnormalities including skeletal malformations of the ear, nose, mouth and larynx including hearing impairment and cleft palate, malformations of the head and facial (craniofacial) area; anomalies of the urinary tract and/or kidney including absent or horse-shoe kidney; or structural abnormalities of the heart (congenital heart defects), mirror movements, webbing of the digits and digital hypoplasia. In addition, in some cases, neurological complications may result due to associated spinal cord injury.KFS may occur as an isolated abnormality or in association with certain syndromes. In many individuals with KFS, the condition appears to occur randomly for unknown reasons (sporadically). In other cases, KFS may be inherited as an autosomal dominant or autosomal recessive trait. Researchers have determined that some cases of KFS are associated with mutations of the GDF6, GDF3, MEOX1 or MYO18B genes. (For further information, please choose “Klippel Feil” as your search term in the Rare Disease Database.)Oculo-auriculo-vertebral spectrum (OAVS) refers to three rare disorders that many clinicians believe to be intimately related to one another and which represent the range of severity of the same disorder. These disorders are apparent at birth (congenital). As the name suggests, they involve malformations of the eyes, ears and spine.Oculo-auriculo-vertebral disorder (OAVD) represents the mildest form of the disorder, while Goldenhar syndrome presents frequently as the most severe form. Hemifacial microstomia appears to be an intermediate form.The disorder is characterized by a wide spectrum of symptoms and physical features that may vary greatly in range and severity from case to case. However, such abnormalities tend to involve the cheekbones, jaw, mouth, ears, eyes, and/or bones of the spinal column (vertebrae). Although, in most cases (about 60%), such malformations affect one side of the body (unilateral), approximately 10 to 33 percent of affected individuals have such malformations on both sides of the body (bilateral), with one side typically more affected than the other (asymmetry). In the majority of such cases, the right side is more severely affected than the left.In most cases OAVS appears to occur randomly, with no apparent cause (sporadic). However, in some cases, family histories suggest autosomal dominant or recessive inheritance. In addition, some researchers suggest that the disorder may be caused by the interaction of many genes, possibly in combination with environmental factors (multifactorial inheritance). (For further information on this disorder, choose “OAVS” as your search term in the Rare Disease Database.)There are additional disorders that may be characterized by skeletal, ocular, auditory, or other abnormalities similar to those potentially associated with Wildervanck syndrome. (For more information on such disorders, choose the exact disease name in question as your search term in the Rare Disease Database.)
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Diagnosis of Wildervanck Syndrome
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Wildervanck syndrome may be detected at birth or during the first year of life based upon a thorough clinical evaluation, identification of characteristic physical findings, and specialized tests. Diagnostic studies may include advanced imaging techniques, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. An MRI uses a magnetic field and radio waves to form detailed cross-sectional images of certain organs and tissues. Such techniques may help to detect and characterize abnormalities of the inner ear, union or fusion of certain bones of the spinal column (e.g., cervical vertebrae), possible impingement of vertebrae on the spinal cord, or other abnormalities potentially associated with the disorder. In addition, in some individuals with Wildervanck syndrome, exploratory surgery may be conducted to detect malformations of the middle ear (exploratory tympanotomy). Additional specialized tests may also be performed to confirm or characterize other abnormalities that may be associated with the disorder (e.g., certain ocular findings, congenital heart defects, renal abnormalities, etc.).
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Diagnosis of Wildervanck Syndrome. Wildervanck syndrome may be detected at birth or during the first year of life based upon a thorough clinical evaluation, identification of characteristic physical findings, and specialized tests. Diagnostic studies may include advanced imaging techniques, such as computerized tomography (CT) scanning or magnetic resonance imaging (MRI). During CT scanning, a computer and x-rays are used to create a film showing cross-sectional images of internal structures. An MRI uses a magnetic field and radio waves to form detailed cross-sectional images of certain organs and tissues. Such techniques may help to detect and characterize abnormalities of the inner ear, union or fusion of certain bones of the spinal column (e.g., cervical vertebrae), possible impingement of vertebrae on the spinal cord, or other abnormalities potentially associated with the disorder. In addition, in some individuals with Wildervanck syndrome, exploratory surgery may be conducted to detect malformations of the middle ear (exploratory tympanotomy). Additional specialized tests may also be performed to confirm or characterize other abnormalities that may be associated with the disorder (e.g., certain ocular findings, congenital heart defects, renal abnormalities, etc.).
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Therapies of Wildervanck Syndrome
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Treatment
The treatment of Wildervanck syndrome is directed toward the specific symptoms and physical findings that are present in each individual. Such therapies 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 may include pediatricians; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); eye specialists (ophthalmologists); hearing specialists (e.g., otologists and audiologists); physicians who diagnose and treat heart abnormalities (cardiologists); surgeons; and/or other health care professionals.Because some affected individuals with abnormal union or fusion of certain cervical vertebrae may have an increased risk of neurological complications, they should be regularly monitored by physicians. In addition, they should avoid activities that may lead to trauma or injury to cervical vertebrae.In some individuals with Wildervanck syndrome, treatment measures may include surgical repair of certain abnormalities. For example, middle ear surgery may be recommended for some individuals with conductive hearing loss. Ocular surgery may help to improve or correct impairment of certain eye movements. In addition, for those with cervical spinal cord compression, surgery may be conducted to correct such compression or associated vertebral instability. Surgical measures may also be recommended for other skeletal, ocular, auditory, cardiac, or other abnormalities potentially associated with Wildervanck syndrome. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.In addition, some affected individuals with hearing impairment may benefit from the use of specialized hearing aids. Other treatment for Wildervanck syndrome is symptomatic and supportive.In some cases, early intervention may be important in ensuring that children with Wildervanck syndrome reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Wildervanck syndrome and their families.
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Therapies of Wildervanck Syndrome. Treatment
The treatment of Wildervanck syndrome is directed toward the specific symptoms and physical findings that are present in each individual. Such therapies 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 may include pediatricians; physicians who diagnose and treat disorders of the skeleton, muscles, joints, and related tissues (orthopedists); eye specialists (ophthalmologists); hearing specialists (e.g., otologists and audiologists); physicians who diagnose and treat heart abnormalities (cardiologists); surgeons; and/or other health care professionals.Because some affected individuals with abnormal union or fusion of certain cervical vertebrae may have an increased risk of neurological complications, they should be regularly monitored by physicians. In addition, they should avoid activities that may lead to trauma or injury to cervical vertebrae.In some individuals with Wildervanck syndrome, treatment measures may include surgical repair of certain abnormalities. For example, middle ear surgery may be recommended for some individuals with conductive hearing loss. Ocular surgery may help to improve or correct impairment of certain eye movements. In addition, for those with cervical spinal cord compression, surgery may be conducted to correct such compression or associated vertebral instability. Surgical measures may also be recommended for other skeletal, ocular, auditory, cardiac, or other abnormalities potentially associated with Wildervanck syndrome. The surgical procedures performed will depend upon the severity of the anatomical abnormalities, their associated symptoms, and other factors.In addition, some affected individuals with hearing impairment may benefit from the use of specialized hearing aids. Other treatment for Wildervanck syndrome is symptomatic and supportive.In some cases, early intervention may be important in ensuring that children with Wildervanck syndrome reach their potential. Special services that may be beneficial include special education, physical therapy, and/or other medical, social, and/or vocational services. Genetic counseling will also be of benefit for individuals with Wildervanck syndrome and their families.
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Overview of Williams Syndrome
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Williams syndrome, also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, a varying degree of mental deficiency, and distinctive facial features that typically become more pronounced with age. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots.Williams syndrome may also be associated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and/or other abnormalities. Cardiac defects may include obstruction of proper blood flow from the lower right chamber (ventricle) of the heart to the lungs (pulmonary stenosis) or abnormal narrowing above the valve in the heart between the left ventricle and the main artery of the body (supravalvular aortic stenosis). Musculoskeletal abnormalities associated with Williams syndrome may include depression of the breastbone (pectus excavatum), abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), or an awkward gait. In addition, most affected individuals have mild to moderate mental retardation; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; a short attention span; and are easily distracted.In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). However, familial cases have also been reported. Sporadic and familial cases are thought to result from deletion of genetic material from adjacent genes (contiguous genes) within a specific region of chromosome 7 (7q11.23).
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Overview of Williams Syndrome. Williams syndrome, also known as Williams-Beuren syndrome, is a rare genetic disorder characterized by growth delays before and after birth (prenatal and postnatal growth retardation), short stature, a varying degree of mental deficiency, and distinctive facial features that typically become more pronounced with age. Such characteristic facial features may include a round face, full cheeks, thick lips, a large mouth that is usually held open, and a broad nasal bridge with nostrils that flare forward (anteverted nares). Affected individuals may also have unusually short eyelid folds (palpebral fissures), flared eyebrows, a small lower jaw (mandible), and prominent ears. Dental abnormalities may also occur including abnormally small, underdeveloped teeth (hypodontia) with small, slender roots.Williams syndrome may also be associated with heart (cardiac) defects, abnormally increased levels of calcium in the blood during infancy (infantile hypercalcemia), musculoskeletal defects, and/or other abnormalities. Cardiac defects may include obstruction of proper blood flow from the lower right chamber (ventricle) of the heart to the lungs (pulmonary stenosis) or abnormal narrowing above the valve in the heart between the left ventricle and the main artery of the body (supravalvular aortic stenosis). Musculoskeletal abnormalities associated with Williams syndrome may include depression of the breastbone (pectus excavatum), abnormal side-to-side or front-to-back curvature of the spine (scoliosis or kyphosis), or an awkward gait. In addition, most affected individuals have mild to moderate mental retardation; poor visual-motor integration skills; a friendly, outgoing, talkative manner of speech; a short attention span; and are easily distracted.In most individuals with Williams syndrome, the disorder appears to occur spontaneously for unknown reasons (sporadically). However, familial cases have also been reported. Sporadic and familial cases are thought to result from deletion of genetic material from adjacent genes (contiguous genes) within a specific region of chromosome 7 (7q11.23).
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Symptoms of Williams Syndrome
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Williams syndrome is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity, even among affected family members. Individuals with Williams syndrome will not have all the symptoms listed below. Some affected individuals do not have heart (cardiac) abnormalities; others may not have elevated levels of calcium in the body (hypercalcemia). In addition, the severity of these symptoms often varies greatly from case to case. Some children with Williams syndrome may have a low birth weight, feed poorly, and fail to gain weight and grow at the expected rate (failure to thrive). Symptoms such as vomiting, gagging, diarrhea, and constipation are common during infancy. Some affected infants may have elevated levels of calcium in their blood (hypercalcemia), leading to loss of appetite, irritability, confusion, weakness, easy fatigability, and/or abdominal and muscle pain. Calcium levels usually return to normal around the age of 12 months. However, in some cases, hypercalcemia may last into adulthood. Linear growth may be delayed during the first four years of life. However, growth spurts usually occur between the age of five and 10 years. Most people with Williams syndrome are less than average height during their adult years.Newborns with Williams syndrome have characteristic “elfin-like” facial features including an unusually small head (microcephaly), full cheeks, an abnormally broad forehead, puffiness around the eyes and lips, a depressed nasal bridge, broad nose, and/or an unusually wide and prominent open mouth. Additional features may include a vertical skin fold on the inner corners of the eyes (epicanthal folds), a small pointed chin, prominent ears, and/or an unusually long vertical groove in the center of the upper lip (philtrum). Some infants with Williams Syndrome may have dental abnormalities including malformed teeth (i.e., hypoplastic enamel), small teeth (microdontia), and upper and lower teeth that do not meet properly (malocclusion).A star-like (stellate) pattern in the iris of the eye may be apparent in about 50 percent of children with this disorder. It is most pronounced in those infants with blue or green eyes. This pattern may be harder to see in those children with darker eyes or it may not be present. Affected infants may also experience inward deviation of the eyes (esotropia) and farsightedness (hyperopia). Children with Williams syndrome are extremely sensitive to sound and may overreact to unusually loud or high-pitched sounds (hyperacusis). Chronic middle ear infections (otitis media) are often present.Motor development, (e.g., sitting and walking) and/or gross and fine motor skills (e.g., picking up an object) may be delayed. The development of secondary sexual characteristics (e.g., pubic hair and underarm hair) may occur prematurely (precocious puberty) in children with this disorder. Breast development and menstruation may occur earlier than expected in females with Williams syndrome. Individuals with this disorder may also have an unusually hoarse voice.Congenital heart defects (CHD) occur in approximately 75 percent of children with Williams syndrome. The most frequent defect is supravalvar aortic stenosis, a condition characterized by the narrowing of the aorta above the aortic valve. The aorta is the main artery of the vascular system. Blood passes from the left ventricle of the heart, through the aortic valve, and into the aorta. In supravalvar aortic stenosis, the area above the aortic valve becomes unusually narrow. Symptoms may include fatigue, pain in the chest, dizziness, unusual heart sounds (murmurs) and/or temporary loss of consciousness (syncope). The amount of narrowing of the aorta may vary among affected individuals. Additional congenital heart defects associated with Williams syndrome may include pulmonary artery stenosis, and/or septal defects. (For more information on these heart defects, see the Related Disorders section of this report.) Abnormally high blood pressure (hypertension) is also common in adults with this disorder.Children with Williams syndrome typically have a personality that is friendly, outgoing, and/or talkative. The appropriate use of language and vocabulary range may be unusually enhanced in some children with this disorder. Mild to moderate mental retardation may occur. However, some children are of average intelligence with severe learning disabilities. Hyperactivity and attention deficit disorder are also common, although most affected individuals have good long-term memory. Some affected individuals may have visual difficulties; they may tend to view a picture in parts as opposed to seeing it as a whole.Older children and adults with Williams syndrome may develop progressive joint problems that limit their range of motion. Skeletal abnormalities such as backward (lordosis), front-to-back (kyphosis), and side-to-side (scoliosis) curvature of the spine may also be present. Some affected individuals may have a sunken breastbone (pectus excavatum) and inward turning of the great toe toward the other toes (hallux valgus). Skeletal and joint abnormalities may result in an abnormal manner of walking (awkward gait). Skeletal abnormalities may become worse as affected individuals age.Additional abnormalities may occur in some individuals with Williams syndrome including kidney (renal) abnormalities, chronic urinary tract infections, an underdeveloped (hypoplastic) thyroid gland, and umbilical or inguinal hernias.
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Symptoms of Williams Syndrome. Williams syndrome is characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity, even among affected family members. Individuals with Williams syndrome will not have all the symptoms listed below. Some affected individuals do not have heart (cardiac) abnormalities; others may not have elevated levels of calcium in the body (hypercalcemia). In addition, the severity of these symptoms often varies greatly from case to case. Some children with Williams syndrome may have a low birth weight, feed poorly, and fail to gain weight and grow at the expected rate (failure to thrive). Symptoms such as vomiting, gagging, diarrhea, and constipation are common during infancy. Some affected infants may have elevated levels of calcium in their blood (hypercalcemia), leading to loss of appetite, irritability, confusion, weakness, easy fatigability, and/or abdominal and muscle pain. Calcium levels usually return to normal around the age of 12 months. However, in some cases, hypercalcemia may last into adulthood. Linear growth may be delayed during the first four years of life. However, growth spurts usually occur between the age of five and 10 years. Most people with Williams syndrome are less than average height during their adult years.Newborns with Williams syndrome have characteristic “elfin-like” facial features including an unusually small head (microcephaly), full cheeks, an abnormally broad forehead, puffiness around the eyes and lips, a depressed nasal bridge, broad nose, and/or an unusually wide and prominent open mouth. Additional features may include a vertical skin fold on the inner corners of the eyes (epicanthal folds), a small pointed chin, prominent ears, and/or an unusually long vertical groove in the center of the upper lip (philtrum). Some infants with Williams Syndrome may have dental abnormalities including malformed teeth (i.e., hypoplastic enamel), small teeth (microdontia), and upper and lower teeth that do not meet properly (malocclusion).A star-like (stellate) pattern in the iris of the eye may be apparent in about 50 percent of children with this disorder. It is most pronounced in those infants with blue or green eyes. This pattern may be harder to see in those children with darker eyes or it may not be present. Affected infants may also experience inward deviation of the eyes (esotropia) and farsightedness (hyperopia). Children with Williams syndrome are extremely sensitive to sound and may overreact to unusually loud or high-pitched sounds (hyperacusis). Chronic middle ear infections (otitis media) are often present.Motor development, (e.g., sitting and walking) and/or gross and fine motor skills (e.g., picking up an object) may be delayed. The development of secondary sexual characteristics (e.g., pubic hair and underarm hair) may occur prematurely (precocious puberty) in children with this disorder. Breast development and menstruation may occur earlier than expected in females with Williams syndrome. Individuals with this disorder may also have an unusually hoarse voice.Congenital heart defects (CHD) occur in approximately 75 percent of children with Williams syndrome. The most frequent defect is supravalvar aortic stenosis, a condition characterized by the narrowing of the aorta above the aortic valve. The aorta is the main artery of the vascular system. Blood passes from the left ventricle of the heart, through the aortic valve, and into the aorta. In supravalvar aortic stenosis, the area above the aortic valve becomes unusually narrow. Symptoms may include fatigue, pain in the chest, dizziness, unusual heart sounds (murmurs) and/or temporary loss of consciousness (syncope). The amount of narrowing of the aorta may vary among affected individuals. Additional congenital heart defects associated with Williams syndrome may include pulmonary artery stenosis, and/or septal defects. (For more information on these heart defects, see the Related Disorders section of this report.) Abnormally high blood pressure (hypertension) is also common in adults with this disorder.Children with Williams syndrome typically have a personality that is friendly, outgoing, and/or talkative. The appropriate use of language and vocabulary range may be unusually enhanced in some children with this disorder. Mild to moderate mental retardation may occur. However, some children are of average intelligence with severe learning disabilities. Hyperactivity and attention deficit disorder are also common, although most affected individuals have good long-term memory. Some affected individuals may have visual difficulties; they may tend to view a picture in parts as opposed to seeing it as a whole.Older children and adults with Williams syndrome may develop progressive joint problems that limit their range of motion. Skeletal abnormalities such as backward (lordosis), front-to-back (kyphosis), and side-to-side (scoliosis) curvature of the spine may also be present. Some affected individuals may have a sunken breastbone (pectus excavatum) and inward turning of the great toe toward the other toes (hallux valgus). Skeletal and joint abnormalities may result in an abnormal manner of walking (awkward gait). Skeletal abnormalities may become worse as affected individuals age.Additional abnormalities may occur in some individuals with Williams syndrome including kidney (renal) abnormalities, chronic urinary tract infections, an underdeveloped (hypoplastic) thyroid gland, and umbilical or inguinal hernias.
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Causes of Williams Syndrome
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Most cases of Williams syndrome appear to occur spontaneously (sporadically) for unknown reasons. However, some familial cases of the disorder have also been reported. Ongoing research indicates that sporadic and familial Williams syndrome result from deletions of genetic material from adjacent genes (contiguous genes) located on the long arm (q) of chromosome 7 (7q11.23). This chromosomal region has been designated “Williams-Beuren Syndrome chromosome region 1” (WBSCR1).Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. 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. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome. According to investigators, 28 genes within the 7q11.23 chromosomal region may play a causative role in Williams syndrome including those known as the ELN (elastin) gene, the LIMK1 (or LIM kinase-1) gene, and the RFC2 (replication factor C, subunit 2) gene. The LIMK1 gene is believed to be involved with visual-spatial problems associated with Williams syndrome.In familial cases, Williams syndrome is inherited as an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from 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 regardless of the sex of the resulting child.Hypercalcemia, which is associated with some cases of Williams syndrome, may occur because of an abnormal sensitivity to vitamin D.
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Causes of Williams Syndrome. Most cases of Williams syndrome appear to occur spontaneously (sporadically) for unknown reasons. However, some familial cases of the disorder have also been reported. Ongoing research indicates that sporadic and familial Williams syndrome result from deletions of genetic material from adjacent genes (contiguous genes) located on the long arm (q) of chromosome 7 (7q11.23). This chromosomal region has been designated “Williams-Beuren Syndrome chromosome region 1” (WBSCR1).Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. 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. For example, “chromosome 11p13” refers to band 13 on the short arm of chromosome 11. The numbered bands specify the location of the thousands of genes that are present on each chromosome. According to investigators, 28 genes within the 7q11.23 chromosomal region may play a causative role in Williams syndrome including those known as the ELN (elastin) gene, the LIMK1 (or LIM kinase-1) gene, and the RFC2 (replication factor C, subunit 2) gene. The LIMK1 gene is believed to be involved with visual-spatial problems associated with Williams syndrome.In familial cases, Williams syndrome is inherited as an autosomal dominant trait. Genetic diseases are determined by two genes, one received from the father and one from 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 regardless of the sex of the resulting child.Hypercalcemia, which is associated with some cases of Williams syndrome, may occur because of an abnormal sensitivity to vitamin D.
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Affects of Williams Syndrome
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Williams syndrome is a rare disorder that affects males and females in equal numbers and infants of any race may be affected. The prevalence of this disorder is approximately one in 10,000-20,000 births in the United States.
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Affects of Williams Syndrome. Williams syndrome is a rare disorder that affects males and females in equal numbers and infants of any race may be affected. The prevalence of this disorder is approximately one in 10,000-20,000 births in the United States.
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Related disorders of Williams Syndrome
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Symptoms of the following disorders can be similar to those of Williams Syndrome. Comparisons may be useful for a differential diagnosis:Noonan syndrome is a rare genetic disorder that is typically evident at birth (congenital). The disorder may be characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low hairline in the back of the head; and short stature. Characteristic abnormalities of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); vertical skin folds that may cover the eyes' inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia); a low nasal bridge; and low-set, prominent, abnormally rotated ears (pinnae). Distinctive skeletal malformations are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart (cardiac) defects, such as obstruction of proper blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Additional abnormalities may include malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, mild mental retardation, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings. (For more information on this disorder, choose “Noonan” as your search term in the Rare Disease Database.)Idiopathic infantile hypercalcemia is characterized by the elevation of blood calcium levels in a newborn for which there is no apparent cause (idiopathic). Symptoms may include loss of appetite (anorexia), irritability, confusion, weakness, easy fatigability, and/or abdominal and muscle pain. Some studies in the medical literature question whether idiopathic infantile hypercalcemia is a separate disorder from Williams Syndrome or if it is a variant of the same disease. Infants with this form of the disease do not have the characteristic facial features or heart defects that are associated with Williams Syndrome.Leprechaunism is a rare progressive inherited endocrine disorder characterized by overgrowth (hyperplasia) of the pancreas, inability to properly utilize insulin (insulin resistance), and excessive amounts of estrogen. Growth retardation begins during fetal development. Symptoms of Leprechaunism may include short arms and legs, large hands, an elfin-like face, sunken cheeks, a pointed chin, a flat broad nose, low-set ears, and widely spaced eyes. Children with Leprechaunism usually have low levels of circulating glucose (hypoglycemia) and elevated levels of insulin (hyperinsulinemia). People with this disorder are not able to use the insulin effectively. (For more information on this disorder, choose “Leprechaunism” as your search term in the Rare Disease Database.)The following disorders may be associated with Williams Syndrome as secondary characteristics. They are not necessary for a differential diagnosis:Pulmonary artery stenosis is a rare congenital heart defect characterized by unusual narrowing of the vessel that carries blood from the right ventricle of the heart to the lungs (pulmonary artery). This defect usually occurs in association with other heart defects, such as septal defects and/or supravalvar aortic stenosis. Symptoms may include unusual heart sounds (murmurs), difficulty breathing, chest pain, and, in severe cases, congestive heart failure.Ventricular septal defects are heart defects that are present at birth (congenital) and can occur in any portion of the ventricular septum. The size and location of the defect determines the severity of the symptoms. Small ventricular septal defects can close on their own or become less significant over time. Moderately-sized defects can cause congestive heart failure resulting in an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), enlargement of the liver, and/or failure to thrive. Large ventricular defects can cause life-threatening complications during infancy. (For more information on this disorder, choose “Ventricular Septal Defects” as your search term in the Rare Disease Database.)Attention Deficit Hyperactivity disorder is a behavioral disorder of childhood characterized by a short attention span, excessive impulsiveness, and inappropriate hyperactivity. This disorder is usually observed before the child reaches the age of 4 years. In some cases, it may not be diagnosed until the child starts school. Symptoms may vary depending on environmental factors and typically worsen when sustained attention is required. Symptoms usually improve with frequent reinforcement in a structured setting without distractions. (For more information on this disorder, choose “Attention Deficit Hyperactivity” as your search term in the Rare Disease Database.)
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Related disorders of Williams Syndrome. Symptoms of the following disorders can be similar to those of Williams Syndrome. Comparisons may be useful for a differential diagnosis:Noonan syndrome is a rare genetic disorder that is typically evident at birth (congenital). The disorder may be characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low hairline in the back of the head; and short stature. Characteristic abnormalities of the head and facial (craniofacial) area may include widely set eyes (ocular hypertelorism); vertical skin folds that may cover the eyes' inner corners (epicanthal folds); drooping of the upper eyelids (ptosis); a small jaw (micrognathia); a low nasal bridge; and low-set, prominent, abnormally rotated ears (pinnae). Distinctive skeletal malformations are also typically present, such as abnormalities of the breastbone (sternum), curvature of the spine (kyphosis and/or scoliosis), and outward deviation of the elbows (cubitus valgus). Many infants with Noonan syndrome also have heart (cardiac) defects, such as obstruction of proper blood flow from the lower right chamber of the heart to the lungs (pulmonary valvular stenosis). Additional abnormalities may include malformations of certain blood and lymph vessels, blood clotting and platelet deficiencies, mild mental retardation, failure of the testes to descend into the scrotum (cryptorchidism) by the first year of life in affected males, and/or other symptoms and findings. (For more information on this disorder, choose “Noonan” as your search term in the Rare Disease Database.)Idiopathic infantile hypercalcemia is characterized by the elevation of blood calcium levels in a newborn for which there is no apparent cause (idiopathic). Symptoms may include loss of appetite (anorexia), irritability, confusion, weakness, easy fatigability, and/or abdominal and muscle pain. Some studies in the medical literature question whether idiopathic infantile hypercalcemia is a separate disorder from Williams Syndrome or if it is a variant of the same disease. Infants with this form of the disease do not have the characteristic facial features or heart defects that are associated with Williams Syndrome.Leprechaunism is a rare progressive inherited endocrine disorder characterized by overgrowth (hyperplasia) of the pancreas, inability to properly utilize insulin (insulin resistance), and excessive amounts of estrogen. Growth retardation begins during fetal development. Symptoms of Leprechaunism may include short arms and legs, large hands, an elfin-like face, sunken cheeks, a pointed chin, a flat broad nose, low-set ears, and widely spaced eyes. Children with Leprechaunism usually have low levels of circulating glucose (hypoglycemia) and elevated levels of insulin (hyperinsulinemia). People with this disorder are not able to use the insulin effectively. (For more information on this disorder, choose “Leprechaunism” as your search term in the Rare Disease Database.)The following disorders may be associated with Williams Syndrome as secondary characteristics. They are not necessary for a differential diagnosis:Pulmonary artery stenosis is a rare congenital heart defect characterized by unusual narrowing of the vessel that carries blood from the right ventricle of the heart to the lungs (pulmonary artery). This defect usually occurs in association with other heart defects, such as septal defects and/or supravalvar aortic stenosis. Symptoms may include unusual heart sounds (murmurs), difficulty breathing, chest pain, and, in severe cases, congestive heart failure.Ventricular septal defects are heart defects that are present at birth (congenital) and can occur in any portion of the ventricular septum. The size and location of the defect determines the severity of the symptoms. Small ventricular septal defects can close on their own or become less significant over time. Moderately-sized defects can cause congestive heart failure resulting in an abnormally rapid rate of breathing (tachypnea), wheezing, an unusually fast heartbeat (tachycardia), enlargement of the liver, and/or failure to thrive. Large ventricular defects can cause life-threatening complications during infancy. (For more information on this disorder, choose “Ventricular Septal Defects” as your search term in the Rare Disease Database.)Attention Deficit Hyperactivity disorder is a behavioral disorder of childhood characterized by a short attention span, excessive impulsiveness, and inappropriate hyperactivity. This disorder is usually observed before the child reaches the age of 4 years. In some cases, it may not be diagnosed until the child starts school. Symptoms may vary depending on environmental factors and typically worsen when sustained attention is required. Symptoms usually improve with frequent reinforcement in a structured setting without distractions. (For more information on this disorder, choose “Attention Deficit Hyperactivity” as your search term in the Rare Disease Database.)
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Diagnosis of Williams Syndrome
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The diagnosis of Williams syndrome may be confirmed by a thorough clinical evaluation that includes a detailed patient history and specialized blood tests that may detect elevated levels of calcium in the blood. Another test, known as fluorescent in situ hybridization [FISH], may be used to determine whether a deletion of one elastin gene on chromosome 7 is present. This deletion is believed to occur in the majority of individuals with Williams Syndrome.
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Diagnosis of Williams Syndrome. The diagnosis of Williams syndrome may be confirmed by a thorough clinical evaluation that includes a detailed patient history and specialized blood tests that may detect elevated levels of calcium in the blood. Another test, known as fluorescent in situ hybridization [FISH], may be used to determine whether a deletion of one elastin gene on chromosome 7 is present. This deletion is believed to occur in the majority of individuals with Williams Syndrome.
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Therapies of Williams Syndrome
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TreatmentInfants with Williams syndrome who have elevated levels of calcium in their blood may be placed on a diet that restricts the intake of vitamin D. Calcium intake may also be restricted. For those children with severe hypercalcemia, treatment with a corticosteroid drug (e.g., prednisone) may be considered on a temporary basis. After the age of about 12 months, calcium levels typically return to normal, even in untreated infants. It is recommended that children with Williams Syndrome also be evaluated by a physician who specializes in endocrine disorders (endocrinologist).Affected children, who have symptoms related to heart defects, should receive a comprehensive evaluation at a hospital that is familiar with these rare congenital heart conditions. Specialized tests may be performed to determine the severity and exact location of congenital heart defects (i.e., EKG, echocardiogram, or cardiac catheterization). Some children with Williams Syndrome who have severe heart defects may require surgical treatment to repair the defect.Centers for developmentally disabled children and special education services in schools may be beneficial for children with Williams syndrome to reach their personal potential. A supportive team approach may also be helpful including speech and language therapy, occupational and physical therapy, social services, and/or vocational training. Music therapy has been advocated, thought not proven, as providing enhanced learning and relief from anxiety in individuals with Williams syndrome.Genetic counseling may be of benefit for people with Williams syndrome and their families. Other treatment is symptomatic and supportive.The American Academy of Pediatrics released a policy statement in May 2001 on the topic, Health Care Supervision for Children with Williams Syndrome (RE0034).
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Therapies of Williams Syndrome. TreatmentInfants with Williams syndrome who have elevated levels of calcium in their blood may be placed on a diet that restricts the intake of vitamin D. Calcium intake may also be restricted. For those children with severe hypercalcemia, treatment with a corticosteroid drug (e.g., prednisone) may be considered on a temporary basis. After the age of about 12 months, calcium levels typically return to normal, even in untreated infants. It is recommended that children with Williams Syndrome also be evaluated by a physician who specializes in endocrine disorders (endocrinologist).Affected children, who have symptoms related to heart defects, should receive a comprehensive evaluation at a hospital that is familiar with these rare congenital heart conditions. Specialized tests may be performed to determine the severity and exact location of congenital heart defects (i.e., EKG, echocardiogram, or cardiac catheterization). Some children with Williams Syndrome who have severe heart defects may require surgical treatment to repair the defect.Centers for developmentally disabled children and special education services in schools may be beneficial for children with Williams syndrome to reach their personal potential. A supportive team approach may also be helpful including speech and language therapy, occupational and physical therapy, social services, and/or vocational training. Music therapy has been advocated, thought not proven, as providing enhanced learning and relief from anxiety in individuals with Williams syndrome.Genetic counseling may be of benefit for people with Williams syndrome and their families. Other treatment is symptomatic and supportive.The American Academy of Pediatrics released a policy statement in May 2001 on the topic, Health Care Supervision for Children with Williams Syndrome (RE0034).
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