Atypical Retinitis Pigmentosa With Macular Sparing in a Patient With Compound Heterozygous ABCA4 Variants: A Case Report and Diagnostic Challenge

一例复合杂合ABCA4变异患者出现黄斑未受累的非典型视网膜色素变性:病例报告及诊断挑战

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Abstract

Inherited retinal dystrophies are a complex group of disorders causing progressive vision loss. The ABCA4 gene is associated with a wide spectrum of retinopathies, most commonly Stargardt disease, which is characterized by central macular degeneration. Retinitis Pigmentosa (RP) is a less common but recognized ABCA4-associated phenotype, typically involving severe, pan-retinal degeneration. A 25-year-old male presented with a 5-year history of nyctalopia and progressive peripheral visual field loss. Best-corrected visual acuity was 1/20 in the right eye and 20/20 in the left eye. Fundus examination revealed pale optic discs, attenuated retinal arteries, and peripheral bone spicule-like pigment deposits, with notable sparing of the macula. Genetic analysis identified compound heterozygous variants in the ABCA4 gene: a known pathogenic variant, c.4793C>A (p.Ala1598Asp), inherited from his father, and a novel variant, c.1769A>G (p.Asp590Gly), inherited from his mother. The novel variant was re-evaluated according to ACMG/AMP guidelines and classified as likely pathogenic based on its absence in population databases, co-segregation with disease, and high in silico prediction scores. This case presents a diagnostic challenge, with a clinical phenotype of macular sparing RP and strong genetic evidence implicating ABCA4. These findings expand the potential phenotypic spectrum of ABCA4-retinopathy and underscore the critical role of genetic testing in diagnosing patients with atypical presentations of inherited retinal disease. Further investigation is needed to fully elucidate the pathogenic mechanism of the novel variant and its contribution to this unusual clinical picture.

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