vitreous traction

Familial Exudative Vitreoretinopathy, EVR2

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 consistent systemic abnormalities have been identified in EVR4.

Genetics

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; 133780, and EVR4; 601813) and X-linked inheritance  have been reported with the former much more common. 

The X-linked form of FEVR (EVR2 described here) results from mutations in the NDP gene and is allelic to Norrie disease (310600).  

Retinopathy of prematurity can be called a phenocopy of FEVR.

Treatment Options

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

References

Kondo, H., Qin, M., Kusaka, S., Tahira, T., Hasebe, H., Hayashi, H., Uchio, E., Hayashi, K. Novel mutations in Norrie disease gene in Japanese patients with Norrie disease and familial exudative vitreoretinopathy. Invest. Ophthal. Vis. Sci. 48: 1276-1282, 2007.

PubMed ID: 
17325173

Chen, Z.-Y., Battinelli, E. M., Fielder, A., Bundey, S., Sims, K., Breakefield, X. O., Craig, I. W. A mutation in the Norrie disease gene (NDP) associated with X-linked familial exudative vitreoretinopathy. Nature Genet. 5: 180-183, 1993.

PubMed ID: 
8252044

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 Options

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

References

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. Epub 2004 Sep 2.

PubMed ID: 
15346351

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.

PubMed ID: 
159881244

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.

Genetics

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.  

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.

References

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.

PubMed ID: 
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.

PubMed ID: 
15981244