Norrie disease with asymmetric retinal severity associated with novel <i>NDP</i> variants

We report three patients from two unrelated families with <i>NDP</i>-associated retinopathy carrying two <i>NDP</i> variants not previously reported in association with ND: c.365A>G, p.(Tyr122Cys), and c.134T>C, p.(Val45Ala).</p> <p>Clinical evaluations included fundus examination, fluorescein angiography, ultrasonography, auditory brainstem response testing, and genetic analysis.</p> <p>Case 1 [p.(Tyr122Cys)] demonstrated asymmetric retinal findings, with retinal dysplasia and avascular retina in one eye and total RD in the fellow eye; retinal photocoagulation was performed in the less severely affected eye.

Case 2 [p.(Val45Ala)] showed bilateral total RD and blindness. Case 3, the younger brother of Case 2 with the same variant, exhibited severe fibroproliferative changes in one eye and a falciform retinal fold with peripheral avascular retina in the fellow eye; retinal photocoagulation was performed in the milder eye. The p.(Tyr122Cys) and p.(Val45Ala) variants were each classified as likely pathogenic according to ACMG/AMP criteria.</p> <p>These cases demonstrate considerable phenotypic variability within the spectrum of <i>NDP</i>-associated retinopathy and highlight the phenotypic overlap between ND and familial exudative vitreoretinopathy, expanding our understanding of genotype -phenotype correlations in <i>NDP</i>-associated retinal disease.</p>