OMIM ID:
Familial Exudative Vitreoretinopathy, EVR4
Alternate Names
Defective Genes
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
Inheritance
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.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission
Autosomal recessive
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.
In order for autosomal recessive disorders to be expressed, offspring generally must inherit two mutations, one from each carrier parent. Carriers with only one mutation, such as the parents, do not have clinical disease. Note that carrier parents can expect that 1 in 4 children (25%) will inherit both mutations and have the disorder, 2 in 4 children (50%) will be carriers like their parents, while 1 in 4 children (25%) inherit neither mutation.