Clinical and Genetic Characterization of RDH12-Retinal Dystrophy in a South American Cohort

Purpose: To characterize the largest cohort of individuals with retinol dehydrogenase 12 (RDH12)-retinal dystrophy to date, and the first one from South America. Design: Retrospective multicenter international study. Subjects: Seventy-eight patients (66 families) with an inherited retinal dystrophy and biallelic variants in RDH12. Methods: Review of clinical notes, ophthalmic images, and molecular diagnosis. Main Outcome Measures: Visual function, retinal imaging, and characteristics were evaluated and correlated. Results: Thirty-seven individuals self-identified as Latino (51%) and 34 as White (47%). Sixty-nine individuals (88%) had Leber congenital amaurosis (LCA)/early-onset severe retinal dystrophy. Macular and midperipheral atrophy were seen in all patients from 3 years of age. A novel retinal finding was a hyperautofluorescent ring in 2 young children with LCA. Thirty-nine patients (50%) had subsequent visits, with mean follow-up of 6.8 ± 7.3 (range, 0–29) years. Eight variants (21%) were previously unreported, and the most frequent variant was c.295C>A, p.Leu99Ile, present in 52 alleles of 32 probands. Individuals with LCA homozygous for p.Leu99Ile (31%) had a later age of onset, a slower rate of best-corrected visual acuity decrease, the largest percentage of patients with mild visual impairment, and were predicted to reach legal blindness at an older age than the rest of the cohort. Conclusions: By describing the largest molecularly confirmed cohort to date, improved understanding of disease progression was possible. Our detailed characterization aims to support research and the development of novel therapies that may have the potential to reduce or prevent vision loss in individuals with RDH12-associated retinal dystrophy. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures.