Decoding pediatric inherited retinal dystrophies: Bridging genetic complexity and clinical heterogeneity

pediatric inherited retinal dystrophies (IRDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive visual function impairment, often manifesting from early childhood. These conditions arise from dysfunction in retinal morphogenesis, phototransduction, and cellular maintenance pathways, involving photoreceptors, the retinal pigment epithelium, and glial systems. This review provides an integrated analysis of the molecular underpinnings, phenotypic variability, diagnostic advancements, and emerging therapeutic avenues for pediatric IRDs. By systematically retracing the literature and leveraging over a decade of laboratory experience, we dissect each major form of pediatric IRD—such as Leber congenital amaurosis, retinitis pigmentosa, Stargardt disease, achromatopsia, and syndromic entities like Usher and Bardet-Biedl syndromes—emphasizing genotype-phenotype correlations and shared pathogenic pathways. Additionally, we discuss next-generation sequencing, advanced bioinformatics, and AI-based diagnostics, along with gene therapy, genome editing, and emerging biotechnologies. By mapping IRDs to molecular networks through Cytoscape and functional genomics, we identify converging pathogenic mechanisms and therapeutic targets. This compendium aims to serve as a reference for clinicians, researchers, and genetic counselors navigating the evolving IRD landscape.