Simultaneous fzd4 and lrp5 mutation in autosomal dominant familial exudative vitreoretinopathy

The purpose of this study was to report simultaneous mutations of FZD4 and LRP5 genes associated with autosomal dominant familial exudative vitreoretinopathy in members of one family.

Case report.

A 16-month-old white boy with a 6-month history of leukocoria was referred for possible retinoblastoma. On examination, the left eye displayed extensive white vitreoretinal fibrosis filling the entire vitreous cavity up to the lens and with additional dystrophic calcification and iris neovascularization. The right eye showed temporal peripheral fibrovascular ridge. Fluorescein angiography showed 360° of peripheral nonperfusion with leakage from the fibrovascular ridge of the right eye and diffuse leakage from the massive vitreoretinal fibrosis and iris neovascularization of the left eye, consistent with familial exudative vitreoretinopathy. Laser photocoagulation of the avascular areas of the right eye was performed with disease stabilization. Clinical examination and genetic testing of the family members demonstrated that the proband and a male sibling had similar clinical findings and simultaneous mutations in the FZD4 and LRP5 genes. Both affected patients had normal bone mineral dual-energy X-ray absorptiometry.

Familial exudative vitreoretinopathy is a retinal vascular disorder usually caused by a single mutation. Rarely, multiple simultaneous mutations can occur and, in this case, result in classic ophthalmic phenotypic and known risk for bone disorders.