A characteristic phenotypic retinal appearance in Norrie disease

Purpose: To describe a striking retinal finding that the authors have only seen in Norrie disease eyes and to determine if a particular genotype corresponds to this dramatic presentation. Methods: This is a retrospective, interventional case report of four patients seen in the clinic over a 1 -year period. All patients had analysis of the Norrie gene by direct sequencing. Results: All patients presented with a similar retinal appearance of dense stalk tissue, globular dystrophic retina, and peripheral avascular retina with pigmentary changes. Each patient was found to have a mutation in the Norrie gene affecting a cystine residue in the cystine knot domain. The mutations are predicted to disrupt the structure of the protein product, norrin, which is required for activation of the Wnt receptor: beta-caten in pathway. Conclusions: No other vitreoretinopathy that the authors have seen demonstrates this characteristic retinal presentation of severe retinal clysplasia. All four patients were found to have mutations in the Norrie gene which alter the cystine knot motif. Mutations affecting this domain appear to have devastating effects on retinal development and indicate phenotype correlates with mutations affecting the cystine knot domain.