Comparative analysis of Alström syndrome and achromatopsia: Genetic insights and ocular distinctions

Abstract PURPOSE: The study compared the clinical features and ocular examination results between patients with Alström syndrome (AS) and those with achromatopsia (ACHM). MATERIALS AND METHODS: Four patients with AS and seven patients with ACHM were analyzed using whole-exome sequencing (and subsequent Sanger sequencing) to identify ALMS1 and ACHM-related disease-causing variants. Genetic profiles and clinical characteristics were assessed, with color fundus imaging, fundus autofluorescence, spectral domain optical coherence tomography (SD-OCT), and electroretinography results compared between the two groups. RESULTS: Fundus imaging revealed progressive retinal changes and extra-macular degeneration in patients with AS but stationary macular alterations in those with ACHM. SD-OCT showed that three patients with AS had outer nuclear layer (ONL) thinning and ellipsoid zone loss beyond the fovea, whereas one patient had severe retinal changes. By contrast, all patients with ACHM exhibited subfoveal ONL thinning. Full-field electroretinography revealed diminished rod and cone responses in three patients with AS but rod function preservation in all patients with ACHM. Furthermore, systemic involvement distinguished AS from ACHM. Notably, one patient with ACHM exhibited a digenic triallelic inheritance pattern. CONCLUSION: This study improves our understanding of the genetic and phenotypic differences between AS and ACHM, thereby increasing diagnostic precision.