Differential Phenotypes in Type I and Type II Pediatric Stickler Syndrome

To compare the ocular and extraocular phenotypes of pediatric patients with Stickler syndrome harboring pathogenic variants in COL2A1 and COL11A1.

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.

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.

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.