Severe congenital ophthalmological malformations and glaucoma might be an important occasional feature in patients with Coffin-Siris syndrome (CSS), especially Coffin-Siris syndrome 9 (CSS9, OMIM #615866) caused by SOX11 mutation. Recently, primary (open-angle) glaucoma was described in two children with the most common form of Coffin-Siris syndrome, CSS1 (OMIM #135900) by ARID1B (AT-rich interaction domain-containing protein 1B) gene mutation. In this article, we present the first report of glaucoma with Coffin-Siris syndrome 9 as well as the first report of secondary glaucoma with any form of Coffin-Siris syndrome. These findings indicate that secondary glaucoma is an occasional finding in patients with Coffin-Siris syndrome. A child with secondary childhood glaucoma and additional ocular manifestations was evaluated and treated at the childhood glaucoma centre in Mainz, Germany. Examination under general anaesthesia revealed ocular anterior segment dysgenesis (ASD) (Peters type iridocorneal dysgenesis) in combination with congenital limbal stem cell deficiency (LSCD), aniridia, and cataract. The patient also had multiple other congenital anomalies and severe developmental delay. To explain his combination of anomalies, molecular genetic analysis from peripheral blood was performed in late 2018 and early 2019. Following normal findings with a panel diagnostic of 18 genes associated with congenital glaucoma, whole exome sequencing was performed and revealed a novel likely pathogenic heterozygous variant c.251G>T, p.(Gly84Val) in the SOX11 gene (SRY-related HMG-box gene 11). The variant had occurred de novo. Thus, the multiple congenital anomalies and developmental delay of the patient represented Coffin-Siris syndrome 9 (CSS9, OMIM #615866). When eye diseases occur in combination with other systemic features, genetic analysis can be seminal. Results indicate that glaucoma is an occasional feature of patients with Coffin-Siris syndrome. As early treatment may improve the visual outcome of patients with glaucoma, we suggest that patients with Coffin-Siris syndrome should receive specific ophthalmological screening.

中文翻译：

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Coffin-Siris 综合征继发性儿童青光眼的首次观察：病例报告和文献综述

严重先天性眼科畸形和青光眼可能是 Coffin-Siris 综合征 (CSS) 患者的一个重要的偶发特征，尤其是由 SOX11 突变引起的 Coffin-Siris 综合征 9 (CSS9, OMIM #615866)。最近，两名患有最常见形式 Coffin-Siris 综合征 CSS1 (OMIM #135900) 的儿童因 ARID1B（富含 AT 相互作用结构域的蛋白 1B）基因突变而患上原发性（开角型）青光眼。在本文中，我们提出了第一份关于 Coffin-Siris 综合征 9 的青光眼报告，以及第一份关于任何形式的 Coffin-Siris 综合征继发性青光眼的报告。这些发现表明，继发性青光眼是 Coffin-Siris 综合征患者中偶然发现的。一名患有继发性儿童青光眼和其他眼部表现的儿童在德国美因茨儿童青光眼中心接受了评估和治疗。全身麻醉下检查发现眼前段发育不全（ASD）（Peters 型虹膜角膜发育不全）合并先天性角膜缘干细胞缺陷（LSCD）、无虹膜和白内障。该患者还患有多种其他先天性异常和严重发育迟缓。为了解释他的异常组合，我们于 2018 年底和 2019 年初对外周血进行了分子遗传学分析。在对与先天性青光眼相关的 18 个基因进行小组诊断后得到正常结果后，进行了全外显子组测序，并揭示了一种新的可能致病杂合变异SOX11 基因（SRY 相关 HMG-box 基因 11）中的 c.251G>T，p.(Gly84Val)。这种变异是从头发生的。因此，患者的多种先天性异常和发育迟缓代表 Coffin-Siris 综合征 9 (CSS9, OMIM #615866)。当眼部疾病与其他全身特征同时发生时，遗传分析可能具有重要意义。结果表明，青光眼是 Coffin-Siris 综合征患者的一个偶然特征。由于早期治疗可能会改善青光眼患者的视力结果，因此我们建议 Coffin-Siris 综合征患者应接受特定的眼科筛查。