Familial Exudative Vitreoretinopathy, EVR1

Clinical Characteristics
Ocular Features: 

The basis for many of the ocular complications likely begins with incomplete development of the retinal vasculature.  Resulting retinal ischemia leads to neovascularization, vitreous hemorrhage and traction, and retinal folds, with some 20% going on to develop rhegmatogenous or traction detachments.  There is, however, considerable clinical variability, even within families, with some infants blind from birth whereas some (41%) adults have only areas of remaining avascularity or evidence of macular dragging.  In fact, some affected individuals are asymptomatic and diagnosed only as part of extensive family studies.  Intraretinal lipid is often seen.  Considerable asymmetry in the two eyes is common.  Secondary cataracts often occur and phthisis bulbi results in some patients.  The clinical picture is sometimes confused with retinopathy of prematurity.

Systemic Features: 

No systemic features have been associated with EVR1 disease.


Familial exudative vitreoretinopathy is the name given to a clinically and genetically heterogeneous group of disorders caused by mutations in several genes.  Both autosomal dominant (EVR1 described here) plus EVR4 (601813) and X-linked inheritance (EVR2; 305390) have been reported with the former much more common.  Similarities in the clinical presentation of Congenital Nonattachment of the Retina may cause diagnotic confusion. 

Mutations in the frizzled-4 gene FZD4 (11q14-q21) have been associated with the EVR1 form of this disease inherited in an autosomal dominant pattern.  Retinopathy of prematurity can be called a phenocopy of FEVR.

Treatment Options: 

Retinal, vitreal, and cataract surgery are indicated in appropriate cases.

Article Title: 


Keser V, Khan A, Siddiqui S, Lopez I, Ren H, Qamar R, Nadaf J, Majewski J, Chen R, Koenekoop RK. The Genetic Causes of Nonsyndromic Congenital Retinal Detachment: A Genetic and Phenotypic Study of Pakistani Families. Invest Ophthalmol Vis Sci. 2017 Feb 1;58(2):1028-1036.

PubMedID: 28192794

Kondo H, Hayashi H, Oshima K, Tahira T, Hayashi K. Frizzled 4 gene (FZD4) mutations in patients with familial exudative vitreoretinopathy with variable expressivity. Br J Ophthalmol. 2003 Oct;87(10):1291-5.

PubMedID: 14507768

Qin M, Hayashi H, Oshima K, Tahira T, Hayashi K, Kondo H. Complexity of the genotype-phenotype correlation in familial exudative vitreoretinopathy with mutations in the LRP5 and/or FZD4 genes. Hum Mutat. 2005 Aug;26(2):104-12.

PubMedID: 15981244