Clinical homogeneity and genetic heterogeneity in Weill-Marchesani syndrome.
Weill-Marchesani syndrome (WMS) is a rare condition characterized by short stature, brachydactyly, joint stiffness, and characteristic eye abnormalities including microspherophakia, ectopia of lens, severe myopia, and glaucoma. Both autosomal recessive (AR) and autosomal dominant (AD) modes of inheritance have been described for WMS. A locus for AR WMS has recently been mapped to chromosome 19p13.3-p13.2 while mutation within the fibrillin-1 gene (15q21.1) was found in one AD WMS family. In order to answer the question of whether or not genetic heterogeneity could be related to a clinical heterogeneity, we reviewed 128 WMS patients from the literature (including 57 AR, 50 AD, and 21 sporadic cases), with a particular attention to clinical features. Statistical analyses using Fischer exact test were used to compare the proportions of 12 clinical parameters between AR and AD patients. There was no significant difference between both groups for myopia, glaucoma, cataract, short stature, brachydactyly, thick skin, muscular build, and mental retardation. Significant results were found for microspherophakia (94% in AR, 74% in AD, Fischer 0.007), ectopia lentis (64% in AR, 84% in AD, Fischer 0.016), joint limitations (49% in AR, 77% in AD, Fischer 0.010), and cardiac anomalies (39% in AR, 13% in AD, Fischer 0.004). Nevertheless, we failed to distinguish AR from AD inheritance in individual cases. These results support the clinical homogeneity but the genetic heterogeneity of WMS.
Département de Génétique et INSERM U393, Hôpital Necker Enfants Malades, 149 rue de Sèvres, 75015 Paris, France.
Laurence
L
Faivre
Hélène
H
Dollfus
Stanislas
S
Lyonnet
Yves
Y
Alembik
André
A
Mégarbané
John
J
Samples
Robert J
RJ
Gorlin
Abdulrahman
A
Alswaid
Josué
J
Feingold
Martine
M
Le Merrer
Arnold
A
Munnich
Valérie
V
Cormier-Daire
D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D004392:Dwarfism / Q000235:genetics; D005124:Eye Abnormalities / Q000235:genetics; D018740:Genetic Heterogeneity; D006130:Growth Disorders / Q000235:genetics; D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics*; D010641:Phenotype; D013577:Syndrome