A Novel Pathogenic Variant of the PRPH2 Gene in Multifocal Pattern Dystrophy Simulating Stargardt Disease: A Case Report and Major Review

Purpose: To present a novel pathogenic variant in PRPH2 in a patient with multifocal pattern dystrophy simulating Stargardt Disease (MPDsSD) and provide a review of the literature summarizing the clinical findings of all presented cases of MPDsSD. Methods: We performed a systematic review of the literature to summarize the clinical findings in patients with MPDsSD. A PubMed search of “(multifocal pattern dystrophy simulating stargardt disease) OR (multifocal pattern dystrophy simulating fundus flavimaculatus) OR (PRPH2 associated retinal dystrophy)” retrieved a total of 152 articles on April 2023. Articles describing the clinical and ophthalmic characteristics of patients with MPDsSD were included. We also describe the case of a 42-year-old male presenting to the clinic with blurry vision and progressively worsening vision in both eyes who was found to have a novel pathogenic variant in the PRPH2 gene. Results: Genetic testing revealed a pathogenic variant in PRPH2, c.640T>C [p.(Cys214Arg)], which provided molecular confirmation of MPDsSD. Moreover, the systematic review, revealed 28 previously reported cases of MPDsSD. The most common presenting symptom among all patients was metamorphopsia (33% of cases). The most common finding on fundus exam was the presence of yellowish fleck-like deposits found in the posterior pole of the retina (83%). All cases of MPDsSD had hyper-autofluorescence of the yellow flecks on fundus autofluorescence. The mean age of onset was 41 years (28 – 65). Mean best corrected visual acuity (BCVA) at presentation was 0.27 (20/37) right eye (OD) and 0.26 (20/36) left eye (OS). Only 48% of the cases reported a known family history of PD. Conclusion: Molecular confirmation can help confirm a clinical suspicion of MPDsSD, as this condition may have overlapping features of other macular dystrophies, most notably Stargardt Disease.