Ophthalmological manifestations in a diverse pediatric population with Type I and Type II Stickler syndrome

Objective: To characterize and compare our cohorts of pediatric patients with type I and type II Sticker syndrome, with a focus on ophthalmological features.

Design: Retrospective cohort study.

Subjects: Twenty-six patients (22 families) with clinical and genetic diagnoses of types I or II Stickler syndrome.

Methods: Review of clinical notes and molecular diagnoses.

Main outcome measures: Ophthalmic and systemic features and responses to laser treatment.

Results: Our cohorts had an equal number of patients with COL2A1-related/Type I and COL11A1-related/Type II Stickler syndrome (n=13; 50%) and include 12 previously unpublished variants. Patients in Type I and II cohorts had similar average ages at presentation and length of follow-up. There were more self-identifying Hispanic patients among the Type II cohort compared to Type I (69% versus 39%, p = 0.145). Individuals with Type II on average had significantly higher myopia compared to those with Type I (p=0.008). Retinal detachment in at least one eye was diagnosed in 39% of the Type I cohort (7 eyes, 5 patients) and 46% of the Type II (7 eyes, 6 patients). Laser prophylaxis was utilized in 69% of patients with Type I and 85% with Type II. Unilateral retinal detachment following laser prophylaxis occurred in one patient with Type I and two with Type II. All identified COL2A1 variants in the Type I cohort are expected to cause disease through haploinsufficiency, and 92% of COL11A1 variants in the Type II cohort are presumed to be in-frame and exert a dominant negative effect, consistent with historical reporting.

Conclusions: The proportion of Types I and II Stickler syndrome are equal in our pediatric population, and patients self-identifying as Hispanic comprised the majority of Type II, supporting the need for additional study of possible under-detection of Type II in diverse populations. Our Type II cohort showed higher myopia and incidence of Pierre Robin sequence, and similar rates of retinal detachment and systemic manifestations compared to the Type I cohort. Our datasets provide important data regarding the safety and short-term effectiveness of laser prophylaxis, but larger and longer-term studies are needed, especially for those with Type II Stickler syndrome.