ImportanceStrabismus is a common ocular disorder of childhood. There is a clear genetic component to strabismus, but it is not known if esotropia and exotropia share genetic risk factors.ObjectiveTo determine whether genetic duplications associated with esotropia are also associated with exotropia.Design, Setting, and ParticipantsThis was a cross-sectional study conducted from November 2005 to December 2023. Individuals with constant or intermittent exotropia of any magnitude or a history of surgery for exotropia were recruited from pediatric ophthalmic practices. Data were analyzed from March to December 2023.ExposureGenetic duplication.Main Outcomes and MeasuresPresence of genetic duplications at 2p11.2, 4p15.2, and 10q11.22 assessed by digital droplet polymerase chain reaction. Orthoptic measurements and history of strabismus surgery were performed.ResultsA total of 234 individuals (mean [SD] age, 19.5 [19.0] years; 127 female [54.3%]) were included in this study. The chromosome 2 duplication was present in 1.7% of patients with exotropia (4 of 234; P = .40), a similar proportion to the 1.4% of patients with esotropia (23 of 1614) in whom it was previously reported and higher than the 0.1% of controls (4 of 3922) previously reported (difference, 1.6%; 95% CI, 0%-3.3%; P < .001). The chromosome 4 duplication was present in 3.0% of patients with exotropia (7 of 234; P = .10), a similar proportion to the 1.7% of patients with esotropia (27 of 1614) and higher than the 0.2% of controls (6 of 3922) in whom it was previously reported (difference, 2.8%; 95% CI, 0.6%-5.0%; P < .001). The chromosome 10 duplication was present in 6.0% of patients with exotropia (14 of 234; P = .08), a similar proportion to the 4% of patients with esotropia (64 of 1614) and higher than the 0.4% of controls (18 of 3922) in whom it was previously reported (difference, 5.6%; 95% CI, 2.5%-8.6%; P < .001). Individuals with a duplication had higher mean (SD) magnitude of deviation (31 [13] vs 22 [14] prism diopters [PD]; difference, 9 PD; 95% CI, 1-16 PD; P = .03), were more likely to have constant (vs intermittent) exotropia (70% vs 29%; difference, 41%; 95% CI, 20.8%-61.2%; P < .001), and had a higher rate of exotropia surgery than those without a duplication (58% vs 34%; difference, 24%; 95% CI, 3%-44%; P = .02).Conclusions and RelevanceIn this cross-sectional study, results suggest that the genetic duplications on chromosomes 2, 4, and 10 were risk factors for exotropia as well as esotropia. These findings support the possibility that esotropia and exotropia have shared genetic risk factors. Whether esotropia or exotropia develops in the presence of these duplications may be influenced by other shared or independent genetic variants or by environmental factors.

中文翻译：

---

外斜视患者中与内斜视相关的拷贝数变异的存在

重要性斜视是儿童时期常见的眼部疾病。斜视有明显的遗传因素，但尚不清楚内斜视和外斜视是否有共同的遗传风险因素。目的确定与内斜视相关的基因重复是否也与外斜视相关。设计、设置和参与者这是一项横断面研究从2005年11月到2023年12月。从儿科眼科诊所招募患有任何程度的持续性或间歇性外斜视或有外斜视手术史的个体。数据分析时间为 2023 年 3 月至 12 月。暴露基因重复。主要结果和措施通过数字液滴聚合酶链式反应评估 2p11.2、4p15.2 和 10q11.22 处基因重复的存在。进行了视力矫正测量和斜视手术史。 结果 本研究共纳入 234 名个体（平均 [SD] 年龄，19.5 [19.0] 岁；127 名女性 [54.3%]）。1.7% 的外斜视患者存在 2 号染色体重复（234 例中有 4 例；磷= .40），与先前报告的内斜视患者（1614 人中的 23 人）的 1.4% 比例相似，并且高于先前报告的对照者（3922 人中的 4 人）的 0.1%（差异为 1.6%；95%）置信区间，0%-3.3%；磷< .001）。3.0% 的外斜视患者存在 4 号染色体重复（234 例中有 7 例；磷= .10），与 1.7% 的内斜视患者（1614 人中的 27 人）的比例相似，并且高于先前报道的对照组（3922 人中的 6 人）的 0.2%（差异，2.8%；95% CI， 0.6%-5.0%；磷< .001）。6.0% 的外斜视患者存在 10 号染色体重复（234 例中的 14 例；磷= .08），与 4% 的内斜视患者（1614 人中的 64 人）的比例相似，并且高于之前报道的对照者（3922 人中的 18 人）的 0.4%（差异为 5.6%；95% CI， 2.5%-8.6%；磷< .001）。具有重复的个体具有较高的平均 (SD) 偏差幅度（31 [13] vs 22 [14] 棱镜屈光度 [PD]；差异，9 PD；95% CI，1-16 PD；磷= .03），更有可能患有持续性（与间歇性）外斜视（70% vs 29%；差异，41%；95% CI，20.8%-61.2%；磷< .001），并且外斜视手术率高于没有重复的患者（58% vs 34%；差异，24%；95% CI，3%-44%；磷= .02). 结论和相关性在这项横断面研究中，结果表明 2、4 和 10 号染色体上的基因重复是外斜视和内斜视的危险因素。这些发现支持内斜视和外斜视具有共同遗传风险因素的可能性。在存在这些重复的情况下是否会出现内斜视或外斜视可能受到其他共享或独立的遗传变异或环境因素的影响。