Drackley Andy, Ralay Ranaivo Hantamalala, Allegretti Valerie, Ing Alexander Y, Rahmani Safa, Blair Michael P, Shapiro Michael J, Bohnsack Brenda L, Rossen Jennifer L
Department of Pathology and Laboratory Medicine, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois; Division of Genetics, Genomics, and Metabolism, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Division of Ophthalmology, Ann and Robert H. Lurie Children's Hospital of Chicago, Chicago, Illinois.
Ophthalmol Retina. 2025 Jul;9(7):690-698. doi: 10.1016/j.oret.2024.12.014. Epub 2024 Dec 14.
To characterize and compare our cohorts of pediatric patients with types I and II Stickler syndrome, with a focus on ophthalmic features.
Retrospective cohort study.
Twenty-six patients (22 families) with clinical and genetic diagnoses of type I or II Stickler syndrome.
Review of clinical notes and molecular diagnoses.
Ophthalmic and systemic features and responses to laser treatment.
Our cohorts had an equal number of patients with COL2A1-related/type I and COL11A1-related/type II Stickler syndrome (n = 13; 50%) and included 12 previously unpublished variants.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 than type I (69% vs. 39%, P = 0.145). Individuals with type II on average had significantly higher myopia compared with those with type I (P = 0.008). Retinal detachment (RD) in at least 1 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 used in 69% of patients with type I and 85% with type II. Unilateral RD after laser prophylaxis occurred in 1 patient with type I and 2 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.
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 underdetection of type II in diverse populations. Our type II cohort showed higher myopia and incidence of Pierre Robin sequence, and similar rates of RD and systemic manifestations compared with the type I cohort. Our data sets 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.
FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
对我们的I型和II型斯-韦二氏综合征儿科患者队列进行特征描述和比较，重点关注眼科特征。
回顾性队列研究。
26例（22个家庭）临床和基因诊断为I型或II型斯-韦二氏综合征的患者。
查阅临床记录和分子诊断结果。
眼科和全身特征以及对激光治疗的反应。
我们的队列中，COL2A1相关/I型和COL11A1相关/II型斯-韦二氏综合征患者数量相等（n = 13；50%），并包括12个此前未发表的变异。I型和II型队列中的患者在就诊时的平均年龄和随访时长相似。II型队列中自我认定为西班牙裔的患者比I型队列更多（69%对39%，P = 0.145）。II型患者的平均近视程度显著高于I型患者（P = 0.008）。I型队列中39%（7只眼，5例患者）、II型队列中46%（7只眼，6例患者）的患者至少一只眼睛被诊断为视网膜脱离（RD）。69%的I型患者和85%的II型患者使用了激光预防性治疗。激光预防性治疗后，I型队列中有1例患者、II型队列中有2例患者发生了单侧RD。I型队列中所有已识别的COL2A1变异预计通过单倍体不足导致疾病，II型队列中92%的COL11A1变异被推测为框内变异并发挥显性负效应，这与既往报道一致。
在我们的儿科人群中，I型和II型斯-韦二氏综合征的比例相等，自我认定为西班牙裔的患者在II型中占多数，这支持了需要对不同人群中可能存在的II型漏检情况进行更多研究。与I型队列相比，我们的II型队列显示出更高的近视率和皮埃尔·罗宾序列发生率，以及相似的RD和全身表现发生率。我们的数据集提供了关于激光预防性治疗安全性和短期有效性的重要数据，但需要更大规模和更长期的研究，特别是针对II型斯-韦二氏综合征患者。
在本文末尾的脚注和披露中可能会发现专有或商业披露信息。
