Drusenoid macular dystrophies in Singaporean Chinese: first report of Doyne honeycomb retinal dystrophy and late-onset retinal degeneration from Southeast Asia.

Abstract

Introduction: We report two ethnic Chinese families affected by distinct drusenoid inherited maculopathies: Doyne Honeycomb Retinal Dystrophy (DHRD) and Late-Onset Retinal Degeneration (L-ORD)-to expand their recognized phenotypic and ethnic spectrum.

Methods: Affected members underwent multimodal ophthalmic imaging, including fundus photography, autofluorescence, optical coherence tomography, and widefield imaging. Genetic testing involved whole exome and targeted sequencing with haplotype and ancestry analysis.

Results: In the DHRD family, two members demonstrated peripapillary drusen, while one also had subretinal drusenoid deposits with minimal progression and no evidence of choroidal neovascularization (CNV). In the L-ORD family, two individuals showed progressive ellipsoid zone loss, outer retinal atrophy, and CNV with spontaneous regression. Pathogenic variants EFEMP1 c.1033C > T (p.Arg345Trp) and C1QTNF5 c.489C > G (p.Ser163Arg) were identified in the DHRD and L-ORD families, respectively. Genetic ancestry revealed no evidence of European admixture.

Conclusion: DHRD and L-ORD, although originally believed to originate from European founder variants, are now established as probable mutational hotspots. We have now uncovered the first known family with DHRD in Southeast Asia, and the first L-ORD family without European heritage. Early recognition of inherited retinal diseases should be considered in patients with atypical drusen and family history of vision loss.