Weill-Marchesani syndrome: Association with fibrillin-1

Purpose. Weill-Marchesani syndrome in this family is inherited as an autosomal dominant trait. A clinical description of the family will be presented as well as chromosome mapping studies. Methods. This family was clinically evaluated for signs of glaucoma, ectopia lentis, myopia, short stature, foot and hand length, joint mobility and skin manifestations. Blood was drawn from normal and affected family members for chromosome mapping studies. Isolated DNA was amplified with microsatellite markers D15S165, D15S144, D15S118, D15S214, D15S132, D15S126, D15S205 as well as MTS2 and G113 which are microsatellite markers located in the fibrillin 1 gene. Results. Six of the seventeen family members in three generations were affected. These six individuals had ectopia lentis, glaucoma, myopia, short stature, and smaller feet and hands compared to the normal family members. However, none of the affected individuals was markedly restricted in movement of their joints. The finding of ectopia lentis in Weill-Marchesani syndrome suggests that fibrillin-1 is a likely candidate gene. Microsatellite markers in and surrounding the fibrillin-1 gene on chromosome 15 were analyzed in all seventeen family members. All of the affected members share the same haplotype. Conclusions. Weill-Marchesani syndrome is transmitted as an autosomal dominant trait in certain families. Fibrillin-1 is a candidate gene for this family; mutation analysis is now being undertaken.