Differential Phenotypes in Type I and Type II Pediatric Stickler Syndrome

Purpose: To compare the ocular and extraocular phenotypes of pediatric patients with Stickler syndrome harboring pathogenic variants in COL2A1 and COL11A1. Methods: This ambispective cohort study included continuous Chinese pediatric patients with genetically confirmed type 1 (COL2A1) and type 2 (COL11A1) Stickler syndrome evaluated between September 2012 and June 2025 at the Zhongshan Ophthalmic Center. Historical clinical records and prospective follow-up data were integrated to analyze phenotypic distributions and risk factors. Results: The study included 94 pediatric probands from 90 unrelated families (COL2A1, n = 64, 53.1% male; COL11A1, n = 30, 46.7% male). The median age at the final visit was 6.40 years (range, 2.03-14.38 years) and 5.95 years (range, 3.22-13.56 years) for the COL2A1 and COL11A1 groups, respectively. Patients with the COL2A1 variants exhibited significantly flatter corneal curvatures in both flat (41.83 ± 0.16 diopters [D] vs. 42.92 ± 0.30 D; P = 0.002) and steep meridians (43.39 ± 0.17 D vs. 45.00 ± 0.35 D; P = 0.001). Furthermore, the COL2A1 group showed a significantly higher prevalence of peripheral retinal lesions, including white without pressure/dark without pressure (51.8% vs. 28.6%, P = 0.031), radial perivascular retinal degeneration (61.6% vs. 0%; P < 0.001), and peripheral vitreoretinal abnormalities (57.1% vs. 24.5%; P = 0.002). The distribution of foveal hypoplasia severity also differed significantly (P = 0.020), with grade I predominating in the COL2A1 group (37.1%) and more advanced cases observed in the COL11A1 group. Conclusions: Pediatric patients with COL2A1-related Stickler syndrome demonstrate significantly flatter corneal curvatures and a greater burden of peripheral retinal lesions compared with those with COL11A1 variants. These findings emphasize the need for genotype-specific clinical monitoring and early fundus screening in this population.