Retinal detachment in Type IX collagen recessive Stickler syndrome

Stickler Syndrome (SS) is associated with eye, joint and orofacial abnormalities. Most cases are dominantly inherited through COL2A1/COL11A1 variants encoding type-II/XI collagen, with patients having up to 78% retinal detachment (RD) risk. Rarer cases of recessive SS have also been identified, associated with pathogenic variants of genes including COL9A1, COL9A2 & COL9A3 encoding type-IX collagen, but there is limited published data on patients' phenotype or RD risk. Our study aimed to investigate RD risk in type-IX recessive SS, determining whether patients would benefit from prophylactic retinopexy. A secondary objective was to explore patient phenotypes, identifying key features which clinicians should identify, leading to earlier diagnosis.

We report 13 cases from 11 families with Type-IX recessive SS, identified from the cohort attending the NHS England Highly Specialised Stickler Syndrome Service (1/1/15-31/12/22). Patients underwent multidisciplinary assessment by ophthalmology, rheumatology and audiology.

6/11 families exhibited previously undescribed genetic variants, and 7 had consanguineous parents. Clinical findings included abnormal vitreous architecture and high myopia. 15.4% of patients developed RD secondary to horseshoe retinal tears, with no cases of bilateral RD or giant retinal tears (GRTs). No patients had cleft palate, and 30.8% had midfacial hypoplasia. Hearing loss was more prevalent (91.7%) than in dominant SS. Arthropathy was uncommon but variable in manifestation.

Ours results do not point to high RD nor GRT incidence in recessive SS, although given the rarity, our numbers are small. Prophylactic retinopexy should only be offered case-by-case for fellow eyes of patients presenting with GRT detachments in their first eye.