Maghsoudi Daniel, Nixon Thomas Rw, Martin Howard, Richards Allan J, McNinch Annie M, Alexander Philip, Poulson Arabella V, Snead Martin P
Vitreoretinal Research Group, John van Geest Centre for Brain Repair, University of Cambridge, Forvie Site, Robinson Way, Cambridge, CB2 0PY, UK.
NHS England Highly Specialised Stickler Syndrome Service, Cambridge University NHS Foundation Trust, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 0QQ, UK.
Eye (Lond). 2025 Jan;39(1):133-138. doi: 10.1038/s41433-024-03393-7. Epub 2024 Oct 15.
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.
斯蒂克勒综合征（SS）与眼部、关节及口面部异常相关。多数病例通过编码II型/ XI型胶原蛋白的COL2A1/COL11A1基因变异呈显性遗传，患者发生视网膜脱离（RD）的风险高达78%。也已发现罕见的隐性SS病例，与包括编码IX型胶原蛋白的COL9A1、COL9A2和COL9A3等基因的致病变异有关，但关于患者表型或RD风险的已发表数据有限。我们的研究旨在调查IX型隐性SS患者的RD风险，确定患者是否能从预防性视网膜固定术中获益。次要目的是探索患者表型，识别临床医生应识别的关键特征，以实现早期诊断。
我们报告了来自11个家庭的13例IX型隐性SS病例，这些病例来自英国国家医疗服务体系（NHS）英格兰高度专业化斯蒂克勒综合征服务队列（2015年1月1日至2022年12月31日）。患者接受了眼科、风湿病科和听力学的多学科评估。
11个家庭中有6个表现出先前未描述的基因变异，7个家庭父母为近亲。临床发现包括玻璃体结构异常和高度近视。15.4%的患者因马蹄形视网膜裂孔继发RD，无双侧RD或巨大视网膜裂孔（GRT）病例。无患者发生腭裂，30.8%有面中部发育不全。听力损失比显性SS更常见（91.7%）。关节病不常见，但表现多样。
我们的结果并未表明隐性SS中RD或GRT的发生率很高，不过鉴于病例罕见，我们的样本量较小。对于第一眼出现GRT脱离的患者，仅应逐例考虑对其健眼进行预防性视网膜固定术。
