Clinical Spectrum and Molecular Characteristics of Inherited Ocular Diseases in a Cohort of Pediatric Patients With Infantile Nystagmus Syndrome.

Abstract

Purpose: Infantile nystagmus syndrome (INS), the most prevalent form of nystagmus in children, often indicates underlying ocular and neurological conditions. Genetic assessment plays a crucial role in clinical management, genetic counseling, and access to emerging gene-based therapies. This study aims to characterize the clinical and genetic landscape of inherited ocular diseases (IODs) in children with INS.

Methods: We retrospectively analyzed clinical and genetic data from 205 unrelated pediatric patients with INS enrolled in an IRB-approved nystagmus registry (2010-2024). All underwent next-generation sequencing (NGS) with targeted gene panels to detect pathogenic variants.

Results: The cohort comprised 117 males and 88 females (mean [SD] age, 8.85 [10.37] years). The most common INS-associated IODs included albinism (32%), Leber congenital amaurosis (LCA) (14%), and achromatopsia (14%). Genetic testing achieved a definitive diagnosis in 85 of 205 patients, yielding a molecular diagnostic rate of 41.5%. A total of 83 pathogenic and likely pathogenic variants were identified across 30 genes. The seven most frequently disease-causing genes-TYR, CNGB3, RPGR, GPR143, ABCA4, OCA2 and FRMD7-accounted for 65% of the genetically solved cases. Additionally, eight genes associated with LCA (AIPL1, CABP4, GUCY2D, IMPDH1, NMNAT1, RDH12, PRPH2, and RPGRIP1) contributed to 15% of these cases.

Conclusions: This study underscores the utility of NGS in diagnosing INS-associated IODs, providing essential insights for targeted interventions and identifying patients as candidates potentially eligible for ongoing gene-based therapy clinical trials.