Última actualización:
June 21, 2018
Años publicados: 1992, 2000, 2003, 2009, 2012, 2015, 2018
NORD gratefully acknowledges Ekaterini Tsilou, MD, Medical Officer, Obstetrics and Pediatric Pharmacology and Therapeutics 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 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.
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.
Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.
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.
Treatment
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:
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Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Newell K, Smith W, Ghoshhajra B, Isselbacher E, Lin A, Lindsay ME. Cervical artery dissection expands the cardiovascular phenotype in FBN1-related Weill-Marchesani syndrome. Am J Med Genet A. 2017 Sep;173(9):2551-2556.
Lim SH, Son JH, Cha SC. Acute angle-closure glaucoma in a highly myopic patient secondary to Weill-Marchesani syndrome: histopathologic lens features. Int Ophthalmol. 2016 Dec;36(6):921-924. Epub 2016 Mar 11.
Guo H, Wu X, Cai K, Qiao Z. Weill-Marchesani syndrome with advanced glaucoma and corneal endothelial dysfunction: a case report and literature review. BMC Ophthalmol. 2015 Jan 9;15:3.
Haji-Seyed-Javadi R, Jelodari-Mamaghani S, Paylakhi SH, Yazdani S, Nilforushan N, Fan JB, Klotzle B, Mahmoudi MJ, Ebrahimian MJ, Chelich N, Taghiabadi E, Kamyab K, Boileau C, Paisan-Ruiz C, Ronaghi M, Elahi E. LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix. Hum Mutat. 2012;33:1182–7.
Kutz WE, Wang LW, Bader HL, Majors AK, Iwata K, Traboulsi EI, Sakai LY, Keene DR, Apte SS. ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. J Biol Chem. 2011;286:17156–67.
Kutz WE, Wang LW, Bader HL, Majors AK, Iwata K, Traboulsi EI, Sakai LY, Keene DR, Apte SS. ADAMTS10 protein interacts with fibrillin-1 and promotes its deposition in extracellular matrix of cultured fibroblasts. J Biol Chem. 2011;286:17156–67.
Dagoneau N, Benoist-Lasselin C, Huber C, et al. ADAMTS10 mutations in autosomal recessive Weill-Marchesani syndrome. Am J Hum Genet. 2004;75:801-6.
Faivre L, Dollfus H, Lyonnet S, et al. Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet. 2003;123:204-7.
Karabiyik L. Airway management of a patient with Weill-Marchesani syndrome. J Clin Anesth. 2003;15:214-6.
INTERNET
Tsilou E, MacDonald IM. Weill-Marchesani Syndrome. 2007 Nov 1 [Updated 2013 Feb 14]. In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1114/ Accessed June 19, 2018.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Weill-Marchesani Syndrome 2; WMS2. Entry No: 608328. Last Edited 09/12/2012. Available at: https://omim.org/entry/608328 Accessed June 19, 2018.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Weill-Marchesani Syndrome 1; WMS1. Entry No: 277600. Last Edited 02/13/2018. Available at: https://omim.org/entry/277600 Accessed June 19, 2018.
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The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
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