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

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.