Weill-Marchesani Syndrome 1

Clinical Characteristics
Ocular Features: 

The Weill-Marchesani phenotype is a rare connective tissue disorder manifested by short stature, brachydactyly, spherophakia and stiff joints.   As many as 94% have spherophakia and 64% have dislocated lenses.  The central corneal thickness is increased.  The small, abnormally shaped lens can migrate anteriorly causing pupillary block glaucoma and sometimes dislocates into the anterior chamber.  This may occur spontaneously or following pharmacologic mydriasis which is sometimes done to relieve the pupillary block.

Systemic Features: 

Short stature in the range of 155 cm in height for men and 145 cm for women is common.  Brachydactyly and stiff joints prevent patients from making a tight fist.   A few patients (13%) have some mild mental deficit but most have normal intelligence.  Cardiac defects include patent ductus arteriosis, pulmonary stenosis, prolonged QT interval mitral valve stenosis, and mitral valve prolapse.  Some heterozygous carriers also are short in stature and may have joint stiffness.

Genetics

Homozygous mutations in the ADAMTS10 gene (19p13.3-p13.2) cause this disorder.  Homozygous mutations in LTBP2 (14q24.3) have also been found in WMS1 and in the Weill-Marchesani-Like syndrome (613195).

Weill-Marchesani syndrome 2 (608328) is a clinically similar syndrome but results from heterozygous mutations in FBN1. Homozygous mutations in ADAMTS17 cause the Weill-Marchesani-Like syndrome (613195) .  It is not always possible to distinguish between the AR and AD forms of the disease using clinical criteria alone.

 

Treatment
Treatment Options: 

Dislocated lenses should be removed if they are interfering with vision or migrate into the anterior chamber.  A peripheral iridotomy should be considered in cases where pupillary block glaucoma occurs.  Long-term mydriasis is not recommended because of the risk of lens dislocation into the anterior chamber.  Chronic open angle glaucoma is a threat and life-long monitoring is recommended.  Measurements of the intraocular pressure should take the increased central corneal thickness into account.  Trabeculectomy should be considered when the pressure cannot be medically controlled.

References
Article Title: 

LTBP2 mutations cause Weill-Marchesani and Weill-Marchesani-like syndrome and affect disruptions in the extracellular matrix

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 Apr 26. doi: 10.1002/humu.22105. [Epub ahead of print] PubMed PMID: 22539340.

PubMed ID: 
22539340

Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome

Faivre L, Dollfus H, Lyonnet S, Alembik Y, M?(c)garban?(c) A, Samples J, Gorlin RJ, Alswaid A, Feingold J, Le Merrer M, Munnich A, Cormier-Daire V. Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet A. 2003 Dec 1;123A(2):204-7. Review.

PubMed ID: 
14598350

References

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 Apr 26. doi: 10.1002/humu.22105. [Epub ahead of print] PubMed PMID: 22539340.

PubMedID: 22539340

Faivre L, Dollfus H, Lyonnet S, Alembik Y, M?(c)garban?(c) A, Samples J, Gorlin RJ, Alswaid A, Feingold J, Le Merrer M, Munnich A, Cormier-Daire V. Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome. Am J Med Genet A. 2003 Dec 1;123A(2):204-7. Review.

PubMedID: 14598350

Razeghinejad MR, Safavian H. Central corneal thickness in patients with Weill-Marchesani syndrome. Am J Ophthalmol. 2006 Sep;142(3):507-8.

PubMedID: 16935606

Jensen AD, Cross HE, Paton D. Ocular complications in the Weill-Marchesani syndrome. Am J Ophthalmol. 1974 Feb;77(2):261-9.

PubMedID: 4812097