Familial exudative vitreoretinopathy (FEVR) is a rare hereditary vitreoretinal disorder characterized by abnormal or incomplete vascularization of the peripheral retina leading to variable clinical manifestations ranging from no effects to minor anomalies, or even retinal detachment with blindness.
The prevalence of FEVR is unknown. It is usually inherited dominantly and many asymptomatic individuals may not come to medical attention as a result of non-penetrance. Males and females appear to be affected equally, except in the X-linked form which only affects males.
The clinical manifestations of FEVR are highly variable among patients in the same family and even between the two eyes. In many patients, retinal abnormalities do not affect vision. Most symptomatic individuals with FEVR present at an early age with peripheral vision disturbances, and flashes or floaters. Major objective signs are similar to retinopathy of prematurity (see this term) and include large angle kappa, retinal detachment, stretched posterior retinal vessels, dragged optic disc, and retinal folds. These ocular anomalies are followed by complications, such as retinal neovascularization and exudates, retinal and vitreous bleeding, vitreoretinal traction, ectopia of the macula, and cataracts. Strabismus and leukocoria are also reported. Patients with severe manifestations are often registered as blind in early infancy. Reduced bone mass with a predisposition to fractures has been reported in some patients (LRP5 mutations).
Mutations in the FZD4 (11q14-q21) or LRP5 (11q13.4) genes have been associated with autosomal dominant FEVR as well as ZNF408 (11p11.2). LRP5 has also been associated with recessive cases. X-linked recessive FEVR is associated with mutations in the NDP gene (Xp11.4-p11.3). Some dominant or recessive cases have been reported to be associated with TSPAN12 (7q31.31). In about 50% of cases, the genetic mutations causing FEVR are unknown.
Early diagnosis is very important in order to avoid serious complications that may develop within the first two decades of life. The diagnosis is based on ophthalmic and general history, including gestational age, birth weight and on ophthalmic examination for the presence of an avascular zone in the peripheral retina by slit lamp biomicroscopy and funduscopy of the peripheral retina in full mydriasis and, if possible, fluorescein angiography. A compatible inheritance pattern within the family may suggest the diagnosis, which can be confirmed by molecular genetic testing.
Retinopathy of prematurity (see this term) is the main differential diagnosis and can generally be ruled out based on gestational age, if available. Other similar conditions include Norrie disease, Coats disease, and persistent hyperplastic primary vitreous (see these terms).
FEVR is genetically and clinically heterogeneous, complicating prenatal diagnosis. Furthermore, requests for prenatal diagnosis of the disease are rare.
The disease most commonly shows autosomal dominant inheritance, and more rarely X-linked recessive or autosomal recessive patterns of inheritance. Significant non-penetrance has been reported. Corresponding genetic counseling should be provided to affected families.
Presymptomatic testing can be offered to families in which the causative mutations have been identified. Standard surgical approaches are used to correct retinal detachment, but results are variable. Prophylactic cryotherapy or argon laser photocoagulation are recommended to reduce new vascularization caused by ischemia. Regular fundus examination is recommended to monitor symptomatic patients. Asymptomatic children and young adults showing avascularity should be monitored annually.
The clinical presentation of FEVR is highly variable. The usual course of the disease has not been well established making the prognosis difficult to ascertain. Progressive loss of vision is reported in severe cases.
Last update: January 2014
- Dr Nienke BOONSTRA
- Dr Rob COLLIN