Abstract
OBJECTIVE: High myopia is a significant risk factor for irreversible vision loss and can occur in isolation or as a component of various syndromes. However, the genetic basis of early-onset high myopia remains poorly understood. We aimed to identify the causative genetic variants for high myopia in a cohort of Slovenian children. METHODS: The study included children referred to a tertiary paediatric ophthalmology centre at the University Eye Clinic in Ljubljana between 2010 and 2022. The participants met the following inclusion criteria: age ≤ 15 years and high myopia ≤-5.0 D before the age of 10 years. Genetic analysis included exome sequencing and/or molecular karyotyping. Participants were categorized based on clinical presentation: high myopia with systemic involvement, high myopia with ocular involvement, and isolated high myopia. RESULTS: Genetic analysis of 36 probands revealed a genetic cause of high myopia in 22 (61.1%) children. Among those with systemic involvement (50.0%), genetic causes were identified in 13 out of 18 children, with Stickler's and Pitt-Hopkins being the most common syndromes. Among cases of high myopia with ocular involvement (38.9%), a genetic cause was found in 8 out of 14 probands, including (likely) pathogenic variants in genes related to retinal dystrophies (CACNA1F, RPGR, RP2, NDP). The non-syndromic ARR3- associated high myopia was identified in the isolated high myopia group. CONCLUSIONS: A genetic cause of high myopia was identified in 61.1% of children tested, demonstrating the value of genetic testing in this population for diagnosis and proactive counseling.