Two Turkish families with type 1 Stickler syndrome carrying novel COL2A1 truncating variants: a case series

To describe the ocular and extraocular findings in two unrelated Turkish families with type 1 Stickler syndrome carrying two novel truncating COL2A1 variants and to emphasize the marked intrafamilial phenotypic variability.

Seven affected individuals from the two families underwent detailed ophthalmic examination including BCVA, slit-lamp biomicroscopy with vitreous phenotype assessment, fundus evaluation, and multimodal retinal imaging. Systemic evaluation included craniofacial, pediatric, orthopedic, and audiological assessments. Index cases underwent clinical exome sequencing; targeted NGS confirmed segregation in family members. Variants were classified as per ACMG criteria.

In Family 1, a novel nonsense COL2A1 variant, c.3910C>T (p.Gln1304Ter), was identified as the father and three sons. Ocular findings ranged from mild myopia and epiretinal membranes to bilateral retinal detachment and macular holes. The membranous vitreous anomaly of type 1 Stickler syndrome was present in all; one child had Pierre Robin sequence and another had cleft palate. In Family 2, a novel nonsense COL2A1 variant, c.3016A>T (p.Lys1006Ter), was detected in the proband along with her mother and brother. The proband had rhegmatogenous retinal detachment; affected relatives showed milder phenotypes including isolated high myopia and high myopia with retinal detachment. Marked intrafamilial phenotypic variability was observed in both families.

These two novel truncating COL2A1 variants expand the mutational spectrum of type 1 Stickler syndrome. This case series illustrates the broad clinical variability of the disease, from isolated high myopia to severe vitreoretinal complications, and supports early molecular diagnosis, family screening, and preventive ophthalmic surveillance.