Familial Exudative Vitreoretinopathy, EVR4

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: 

Osteoporosis and endosteal hyperostosis has been reported among individuals with mutations in LRP5.

Genetics

The EVR4 form of FEVR results from mutations in the LRP5 gene (11q13.4) and the clinical features may be seen in both heterozygotes and homozygotes.  Thus the disease is inherited in both autosomal dominant and autosomal recessive patterns.  The osteoporosis-pseudoglioma syndrome (259770) is allelic to this condition.

Mutations in the FZD4 gene cause a phenotypically indistinguishable condition (EVR1; 133780) but is always inherited in an autosomal dominant pattern.  There is also an X-linked form (EVR2) caused by a mutation in NDP (305390).

Retinopathy of prematurity can be called a phenocopy of FEVR.

Treatment
Treatment Options: 

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

References
Article Title: 

References

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: 159881244

Jiao X, Ventruto V, Trese MT, Shastry BS, Hejtmancik JF. Autosomal recessive familial exudative vitreoretinopathy is associated with mutations in LRP5. Am J Hum Genet. 2004 Nov;75(5):878-84.

PubMedID: 15346351