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Familial Exudative Vitreoretinopathy, EVR2

OMIM ID:

X-linked recessive

Familial Exudative Vitreoretinopathy, EVR2

Alternate Names

FEVRX
X-linked FEVR
EVR2

Defective Genes

NDP

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 EVR2.

Genetics

Inheritance

Familial exudative vitreoretinopathy is the name given to a clinically and genetically heterogeneous group of disorders caused by mutations in several genes.  Autosomal dominant (e.g., EVR1; 133780), and X-linked inheritance (this condition) 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 (Xp11.3) and is allelic to Norrie disease (310600).

Retinopathy of prematurity can be called a phenocopy of FEVR.

Pedigree

X-linked recessive, carrier mother

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children.  If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome.  However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease.  Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.

Image
Sample pedigree of X-linked recessive inheritance, carrier mother

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the mother, she usually does not have the disease since the normal X chromosome without the mutation neutralizes the mutation in the abnormal X chromosome. However, half her sons will inherit the mutation-containing X chromosome and therefore have the X-linked disease. Half the daughters will inherit the mutation-bearing X chromosome and are usuallly healthy 'carriers'.

X-linked recessive, father affected

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children.  If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene.  His sons only receive his Y chromosome and thus are all normal.  However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'.  Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.

Image
Sample pedigree of X-linked recessive inheritance, father affected

X-linked disorders are caused by a mutation on the X chromosome and both sexes can pass this to their children. If the mutation is in a recessive gene and carried by the father, he has the disease since his only X chromosome is mutant and he has no normal X to blunt the effects of the abnormal gene. His sons only receive his Y chromosome and thus are all normal. However, all his daughters receive his one and only X chromosome and will be healthy 'carriers'. Thus such males will have no affected children but half their grandsons from those daughters will have the same disease as he does.

Treatment & Management

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

Publications

Displaying 1 - 2 of 2

A mutation in the Norrie disease gene (NDP) associated with X–linked familial exudative vitreoretinopathy

PubMedID: 8252044

Novel Mutations in Norrie Disease Gene in Japanese Patients with Norrie Disease and Familial Exudative Vitreoretinopathy

PubMedID: 17325173