A Novel Pathogenic Variant in the RDH5 Gene in a Patient with Fundus Albipunctatus and Severe Macular Atrophy

Purpose To report a novel 11-cis retinol dehydrogenase gene (RDH5) variant discovered in a 57-year-old male with fundus albipunctatus (FA) complicated by severe macular atrophy. Methods The patient was evaluated with a complete ophthalmic examination, optical coherence tomography (OCT), color fundus photography, green wavelength fundus autofluorescence, visual field testing, full-field ERG (ffERG), and multifocal ERG (mfERG). Genetic analysis investigating gene variants involved in inherited retinal disorders was performed. Results The patient presented with a rapid decline in visual acuity and a history of poor night vision. On fundoscopy, he exhibited a phenotype characteristic of FA accompanied by severe macular atrophy bilaterally. Heterozygous variants in the RDH5 gene were identified, including a novel missense variant, c.814_815del (p.Leu272Aspfs∗63), and a known pathogenic nonsense variant, c.160C > T (p.Arg54∗). Fundus autofluorescence demonstrated bull's eye maculopathy and hyperautofluorescent perifoveal rings bilaterally. OCT showed foveal atrophy of the outer retina and scattered hyper-reflective lesions in the peripheral macula. The ffERG results showed a severely diminished scotopic and photopic response. The mfERG results demonstrated minimal response in the central macula. Conclusions Fundus albipunctatus is a rare, congenital form of stationary night blindness caused almost exclusively by the RDH5 gene. This patient's clinical presentation, diagnostic studies, and genetic testing confirmed the diagnosis of FA. Additionally, he exhibited severe macular atrophy, not typically found in FA. Two RDH5 gene variants were identified, one of which is the novel variant, c.814_815del (p.Leu272Aspfs∗63). We suggest that this RDH5 genotype may be associated with a more progressive phenotype of FA contributing to macular atrophy.