• Disease Overview
  • Synonyms
  • Signs & Symptoms
  • Causes
  • Affected Populations
  • Disorders with Similar Symptoms
  • Diagnosis
  • Standard Therapies
  • Clinical Trials and Studies
  • References
  • Programs & Resources
  • Complete Report

Weill Marchesani Syndrome

Print

Last updated: June 21, 2018
Years published: 1992, 2000, 2003, 2009, 2012, 2015, 2018


Acknowledgment

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.


Disease Overview

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.

  • Next section >
  • < Previous section
  • Next section >

Synonyms

  • congenital mesodermal dysmorphodystrophy
  • mesodermal dysmorphodystrophy, congenital
  • spherophakia-brachymorphia syndrome
  • WMS
  • WM syndrome
  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Signs & Symptoms

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.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Causes

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.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Affected populations

Weill Marchesani syndrome is a very rare disorder. The prevalence has been estimated to be approximately 1 in 100,000.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Diagnosis

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.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Standard Therapies

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.

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

Clinical Trials and Studies

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
Email: prpl@cc.nih.gov

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/

  • < Previous section
  • Next section >
  • < Previous section
  • Next section >

References

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.

  • < Previous section
  • Next section >

Programs & Resources

RareCare® Assistance Programs

NORD strives to open new assistance programs as funding allows. If we don’t have a program for you now, please continue to check back with us.

Additional Assistance Programs

MedicAlert Assistance Program

NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.

Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/

Rare Disease Educational Support Program

Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORD’s mission.

Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/

Rare Caregiver Respite Program

This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.

Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/

Patient Organizations


National Organization for Rare Disorders