Familial Exudative Vitreoretinopathy, Autosomal Dominant – RETIRED CHAPTER, FOR HISTORICAL REFERENCE ONLY

NOTE: THIS PUBLICATION HAS BEEN RETIRED. THIS ARCHIVAL VERSION IS FOR HISTORICAL REFERENCE ONLY, AND THE INFORMATION MAY BE OUT OF DATE.

Clinical characteristics: Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is characterized by failure of peripheral retinal vascularization. The visual problems and variable phenotype associated with adFEVR result from secondary complications caused by retinal ischemia. The retinal avascularity is probably present from birth and generates sequelae that stabilize in early adult life or progress in later life. Expressivity may be asymmetric and is highly variable, ranging from mild or asymptomatic to severe (e.g., registered as blind) within the same family.

Diagnosis/testing: The diagnosis of adFEVR is based on a family history compatible with autosomal dominant inheritance and bilateral peripheral retinal avascularity, seen temporally, by indirect ophthalmoscope and scleral indentation, or by fundus fluorescein angiography. Pathogenic variants in one of three genes are known to be associated with adFEVR: FZD4, encoding the protein frizzled-4; LRP5, encoding low-density lipoprotein receptor-related protein 5; and TSPAN12, encoding tetraspanin-12. Pathogenic variants in these genes are responsible for fewer than 50% of adFEVR cases. Another locus, EVR3, has been mapped; the gene is not known.

Management: Treatment of manifestations: Prophylactic cryotherapy or argon laser photocoagulation to induce regression of new vessel growth caused by ischemia resulting from retinal avascularity; treatment is similar for retinal holes and areas of retinal exudate to prevent retinal detachment; rhegmatogenous retinal detachments produced by retinal traction are repaired surgically using conventional methods and exudative retinal detachments may be stabilized with cryotherapy, but prognosis is guarded for both.

Prevention of secondary complications: Reduced bone density would be expected to benefit from drugs used to treat osteoporosis; however, long-term follow-up data are not yet available.

Surveillance: Regular fundus examination in children to evaluate for neovascularization, traction, or exudate; review of individuals with retinal traction at intervals determined by the clinical findings.

Evaluation of relatives at risk: Fundus examination and fundus fluorescein angiography to identify characteristic lesions to allow early treatment.

Genetic counseling: Autosomal dominant FEVR is inherited in an autosomal dominant manner. Offspring of an affected individual are at a 50% risk of inheriting the pathogenic variant, but many individuals with adFEVR can be asymptomatic because of reduced penetrance. Prenatal testing is possible if the pathogenic variant has been identified in the family.