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NORD is very grateful to Ekaterini Tsilou, MD, Medical Officer, Obstetrics and Pediatric Pharmacology Branch, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, for assistance in the preparation of this report.
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.
The symptoms and findings associated with Weill-Marchesani syndrome vary from case to case. 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) and a narrowed pulmonary valve (pulmonary stenosis).
Weill Marchesani syndrome follows autosomal recessive or autosomal dominant inheritance.
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 will be a carrier for the disease but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
The ADAMTS10 gene has been found to be associated with autosomal recessive Weill Marchesani syndrome.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
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. Most individuals with autosomal dominant Weill Marchesani syndrome have an affected parent. The risk of passing the abnormal gene from affected parent to offspring is 50% for each pregnancy. The risk is the same for males and females.
The FBN1 gene has been found to be associated with autosomal dominant Weill Marchesani syndrome in one family.
Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.
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 as an autosomal dominant trait. 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.)
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.
The 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.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
For information about clinical trials sponsored by private sources, contact:
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Report last updated: 2012/03/19 00:00:00 GMT+0