ZNF408

Familial Exudative Vitreoretinopathy, EVR6

Clinical Characteristics
Ocular Features: 

Clinical features of this type of exudative retinopathy are based upon the findings in a single large Dutch pedigree containing 16 affected individuals.  The age of onset is unknown but this condition has been described in a 3 year old.  Characteristics of FEVR6 are often seen in individuals during the second or third decades when decreasing vision becomes a challenge.  While some individuals can have normal acuity, others have severe vision loss, often to finger-counting range.

Ocular findings are limited to the fundus consisting of areas of hypo- or hyperpigmentation, dragging of the macula, peripheral retinal avascularity, leaky and stretched capillaries, and exudates.  There may be falciform retinal folds and detachments.  Some patients have white masses of fibrous tissue in or overlying the retina.  Cataracts have been described in several patients.

Systemic Features: 

No systemic abnormalities have been reported.

Genetics

FEVR6 results from heterozygous mutations in the ZNF408 gene (11p11.2).  Homozygous mutations in the same gene are responsible for retinitis pigmentosa 72 (616469).

Pedigree: 
Autosomal dominant
Treatment
Treatment Options: 

Retinal detachment surgery, while technically difficult, may provide some benefit.

References
Article Title: 

ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature

Collin RW, Nikopoulos K, Dona M, Gilissen C, Hoischen A, Boonstra FN, Poulter JA, Kondo H, Berger W, Toomes C, Tahira T, Mohn LR, Blokland EA, Hetterschijt L, Ali M, Groothuismink JM, Duijkers L, Inglehearn CF, Sollfrank L, Strom TM, Uchio E, van Nouhuys CE, Kremer H, Veltman JA, van Wijk E, Cremers FP. ZNF408 is mutated in familial exudative vitreoretinopathy and is crucial for the development of zebrafish retinal vasculature. Proc Natl Acad Sci U S A. 2013 Jun 11;110(24):9856-61.

PubMed ID: 
23716654

Retinitis Pigmentosa 72

Clinical Characteristics
Ocular Features: 

The history and fundus findings are typical for classic retinitis pigmentosa with onset of symptoms in the 4th and 5th decades or earlier. Salt and pepper pigmentation may also be present. These consist of night blindness, decreased visual acuity, and constriction of visual fields.  The fields are constricted to 10-30 degrees, and vision ranges from 20/25 to 20/40.  Optic pallor is often present, the retinal vessels are narrowed and bone-spicule pigmentation has been described.  Vitreous 'condensation' sufficient to obscure fundus details may be present.  ERG responses are absent or substantially reduced.  Heterozygotes have no symptoms or fundus abnormalities.

Systemic Features: 

No systemic features have been described.

Genetics

Homozygous mutations in the ZNF408 gene (11p11.2) are responsible for this condition.  The product of this gene is a transcription factor highly expressed in fetal and adult retina and plays a role in vasculogenesis.

Heterozygous mutations in the same gene cause familial exudative vitreoretinopathy (FEVR6) (616468) described in one family with significant vitreal and retinal vascular disease.

Pedigree: 
Autosomal recessive
Treatment
Treatment Options: 

No treatment is available for the basic disease.  Tinted lenses may provide some benefit.

References
Article Title: 

Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations

Avila-Fernandez A, Perez-Carro R, Corton M, Lopez-Molina MI, Campello L, Garanto A, Fernandez-Sanchez L, Duijkers L, Lopez-Martinez MA, Riveiro-Alvarez R, Da Silva LR, Sanchez-Alcudia R, Martin-Garrido E, Reyes N, Garcia-Garcia F, Dopazo J, Garcia-Sandoval B, Collin RW, Cuenca N, Ayuso C. Whole-exome sequencing reveals ZNF408 as a new gene associated with autosomal recessive retinitis pigmentosa with vitreal alterations. Hum Mol Genet. 2015 Jul 15;24(14):4037-48.

PubMed ID: 
25882705
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