Expanding the Clinical Spectrum of CEP290 Variants: A Case Report on Non-Syndromic Retinal Dystrophy with Mild Phenotype

Background/Objectives: Biallelic pathogenic variants in the CEP290 gene are typically associated with severe, early-onset inherited retinal dystrophies (IRDs) in both syndromic and non-syndromic forms. This study highlights the phenotypic variability of CEP290-related non-syndromic IRDs, focusing on two siblings with biallelic CEP290 variants. One sibling presents with a milder phenotype, expanding the known spectrum of CEP290-related IRDs and emphasizing the importance of personalized clinical monitoring; Methods: Whole-exome sequencing (WES) was used to identify CEP290 pathogenic variants in the siblings. Comprehensive ophthalmologic evaluations were performed to assess the severity and progression of retinal degeneration; Results: Both siblings were found to carry compound heterozygous pathogenic variants in CEP290, inherited in trans. Clinical evaluations revealed significantly preserved retinal function in the sister, whereas the brother exhibited a more aggressive and progressive retinal dystrophy; Conclusions: This study expands the phenotypic spectrum of non-syndromic CEP290-related IRDs, demonstrating that biallelic CEP290 variants can result in a wide range of severity, from mild to severe. These findings highlight the need for personalized monitoring and tailored management strategies in CEP290-related IRDs.