关键词: 早发高度近视, Stickler综合征, LOXL3基因

Abstract: Objective To analyze the genotype and phenotype of patients with early-onset high myopia (eoHM) caused by pathogenic variants in LOXL3 gene. Design Retrospective case series. Participants A total of 17 patients with eoHM carrying pathogenic variants in LOXL3 gene, collected from Beijing Tongren Hospital (3 cases) and cases previously reported (14 cases). Methods Patients in Beijing Tongren Hospital underwent ophthalmic (BCVA, optometry, color fundus photography, retinal OCT) and systemic examinations (oral, facial, joint and hearing). Reported cases were recorded for the aforementioned information. Patients were diagnosed with Stickler syndrome (SS) or simple eoHM based on the presence of extra-ocular phenotypes. Main Outcome Measures Pathogenic gene variants, age of examination, spherical equivalent refraction (SER), extra-ocular phenotypes. Results Of the 17 patients, 11 were simple eoHM and 6 were SS. The median age at diagnosis was 4.0 years (simple eoHM) and 9.5 years (SS). The average SER was (-15.36±15.50) D (simple eoHM) and (-9.78±3.90) D (SS). The degree of myopia in simple eoHM patients was significantly greater than that in SS patients (P<0.001), and their myopia got worsens with age (P=0.0001), their visual impairment was obviously more severe than that in SS patients (P=0.026). SS patients exhibit extra-ocular manifestations in addition to ocular phenotypes, which were mainly midfacial hypoplasia. 16 pathogenic variants in LOXL3 gene were detected in this group of patients, including 9 missense variants, 6 truncation variants (5 frameshift and 1 nonsense), and 1 spliceing variant. All the simple eoHM patients carried at least one truncation variant, while the SS patients mainly carried missense variants. All patients in this group exhibited varying degrees of myopic fundus manifestations, but the parapapillary atrophy was narrow and thin. 3 simple eoHM patients had a history of retinal detachment. Conclusion This study expanded the variant spectrum of LOXL3 gene and found that patients carrying truncation variants of LOXL3 gene had severe high myopia and a high risk of retinal detachment, while patients carrying missense variants were prone to develop extra-ocular syndrome phenotypes. (Ophthalmol CHN, 2025, 34: 18-24)

Key words: early-onset high myopia, Stickler syndrome, LOXL3 gene