Stickler syndrome type 1: case series and new genetic variants

Stickler syndrome is a hereditary connective tissue disease with variable eye, auditory and musculoskeletal involvement. Its multi-organ signs require various specialists to be aware of it. We present a case series illustrating clinical variability and the presence of undescribed genetic variants.

Descriptive observational study of patients with clinical and genetic diagnosis of Stickler syndrome evaluated in a specialized hospital setting. Clinical signs and identified genetic variants were analyzed, as well as intra- and inter-familial variability in cases with shared mutations.

The cohort comprised 18 patients carrying pathogenic or likely pathogenic heterozygous variants in the COL2A1 gene. Six distinct variants were identified, five of which have not been reported in other patients. Ophthalmological signs were the most prevalent clinical features, with myopia and retinal detachment observed in 67% of patients, followed by hearing loss (44%) and early-onset osteoarthritis (44%). Ocular signs exhibited the earliest age at onset. Intrafamilial analyses revealed relative phenotypic homogeneity among individuals harboring the same mutation, whereas marked differences were observed between families, suggesting distinct clinical profiles associated with specific genetic variants.

This case series confirms the marked clinical heterogeneity of Stickler syndrome and identifies novel disease-causing variants in COL2A1. The findings support the presence of a partial genotype-phenotype correlation, which may inform clinical surveillance and risk stratification, particularly with regard to ophthalmological complications.