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Familial exudative vitreoretinopathy - The exudative vitreoretinopathies (EVR) are a group of genetically heterogenous familial disorders believed to be caused by arrested peripheral retinal angiogenesis/vasculogenesis or retinal vascular differentiation. Clinical features vary, even within families, from blindness in childhood to patients with few or no visual problems who may be diagnosed only following fluorescein angiography. Eye findings reported in EVR include: decreased visual acuity, blindness, falciform retinal folds, vitreoretinal traction, partial or total retinal detachment, macular ectopia, retinal exudates, vitreous detachment, subcapsular opacities, peripheral retinal avascularization, retinal neovascularization and vitreous hemorrhage. Penetrance in EVR is high and may reach 100%. Several genes and loci have been linked to EVR and inheritance may be autosomal dominant, autosomal recessive or X-linked.

EVR1 (MIM 133780) is an autosomal dominant form of familial exudative vitreoretinopathy caused by mutations in the FZD4 gene on chromosome 11q14. The FZD4 gene is a member of the 7-transmembrane domain family that is involved with retinal angiogenesis via the Wnt signaling pathway. Studies suggest that FZD4 mutations account for approximately 20-40% of EVR cases.

EVR2 (MIM 305390) is an X-linked form of familial exudative vitreoretinopathy caused by mutations in the NDP gene, which is also associated with Norrie disease (MIM 310600). There is possibly a second locus for EVR on the X chromosome. Mutations in NDP probably account for 10% or less of EVR cases. EVR3 (MIM 605750) is linked to a locus on chromosome 11p13-p12 in one family. However, no gene has been identified.

EVR4 (MIM 601813) is caused by mutations in the LRP5 gene on chromosome 11q13. Inheritance may be autosomal recessive or autosomal dominant. The low density lipoprotein receptor-related protein 5 interacts with FZD4 and is also a receptor involved in Wnt signaling. In one instance, an FZD4 mutation and an LRP5 mutation have been detected in the same patient. Many patients with either autosomal recessive or dominant EVR4 also have low bone mass. In these patients, their phenotype may overlap with osteoporosis-pseudoglioma syndrome (OPPG; MIM 259770) an autosomal recessive disorder also characterized by early vision loss and caused by LRP5 mutations. It has been suggested that EVR4 and OPPG represent a phenotypic spectrum rather than distinct disorders. Autosomal dominant LRP5 mutations are thought to account for about 15% of EVR cases.

EVR5 (MIM 613310) is an autosomal dominant disorder caused by mutations in the TSPAN12 gene on chromosome 7q13. Mutations in this gene are thought to account for 3-10% of EVR cases.