We report 13 patients from 11 families with Type IX collagen recessive SS, with our key finding being that 15.4% of patients developed retinal detachment with no GRTs, at a mean age of 30. This result, taken in isolation, would suggest that prophylactic retinopexy against giant retinal tear detachment is unlikely to have been effective in these patients. However, more than half the patients in this series are under 18 years of age, and so the lifetime risk of RDs and GRTs remains to be determined.
Other clinical features including high myopia and a hypoplastic vitreous were seen in most of our patients, in keeping with findings from Nixon et al., 2022 (ref. 19) Interestingly, the 30.8% incidence of facial abnormalities and lack of cleft palates in both our cohort and the wider literature may indicate a significant difference from autosomal dominant SS, where cleft palate is a relatively common finding either in isolation or as part of the Pierre Robin Sequence.13
Hearing loss has previously been reported as a consistent feature of type IX collagen recessive SS, present for every patient with the condition. Our cohort exhibited an 84.6% incidence of hearing loss, primarily sensorineural hearing loss requiring hearing aids. However, 15.4% of patients had completely normal hearing, suggesting hearing loss cannot be considered a consistent feature of the condition. It does appear to be more common in recessive SS than type 1 SS, where only half of patients show hearing impairment.7
Joint problems were reported in 30.8% of patients, broadly in line with the 22.7% incidence reported by Nixon et al., 2022 (ref. 19) for recessive Stickler. However, it is important to note that joint pain can vary significantly between patients – the majority of patients in this series had no or minimal symptoms, whilst two had severe arthropathy. Whilst 8-I exhibited severe arthropathy requiring a wheelchair, their relative with an identical variant of COL9A3 (8-II) had no joint problems other than mild scoliosis, highlighting the phenotypic heterogeneity of recessive Stickler Syndrome. As a result, joint problems are an inconsistent diagnostic tool for recessive SS and correlate poorly with other non-rheumatological symptoms of the condition. Furthermore, it is again important to note that since the majority of our patients are under 18 (median age 14), it is possible that the incidence of joint problems would increase over time within the cohort. Type IX collagen recessive SS does appear to be associated with a lower incidence of skeletal abnormalities, with nearly 50% of children with dominant SS exhibiting abnormalities on knee and spinal radiographs.12
This series suggests that recessive Stickler Syndrome may have a lower risk of retinal detachment than the more common dominant subtypes of the condition, but this can only be confirmed or refuted on further longitudinal study. Until such data is available prophylactic retinopexy cannot be recommended based on current evidence, or should be offered on a case-by-case basis according to individual risk assessment and informed patient consent. Our results also suggest that recessive SS is associated with similar facial abnormalities but may have a lower risk of cleft palate and arthropathy, but a higher incidence of hearing loss than dominant SS. Recognition of the distinct features of recessive SS are important in prompting clinicians to request an appropriate molecular genetic analysis, leading to early diagnosis and allowing patients to receive appropriate counselling and multi-disciplinary management. Patients must also be warned of the early warning symptoms of posterior vitreous detachment and retinal detachment, enabling early surgical intervention as required. The high incidence of hearing loss and potential for significant joint problems in these patients is also important to note. A diagnosis of SS should be considered by clinicians seeing young patients with congenital hearing loss, joint problem, and high myopia, particularly recessive SS if there is a history of consanguinity. Early diagnosis is particularly important as the risk of both deafness and blindness secondary to retinal detachment provides a significant risk of dual-sensory impairment.