Department of Ophthalmology, University Medical Centre of the Johannes Gutenberg University Mainz, Langenbeckstr. 1, D - 55131, Mainz, Germany.
Institute of Human Genetics, University Medical Centre of the Johannes Gutenberg University Mainz, Mainz, Germany.
BMC Ophthalmol. 2021 Jan 11;21(1):28. doi: 10.1186/s12886-020-01788-0.
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.
严重的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，在最常见的 Coffin-Siris 综合征（CSS1，OMIM#135900）的两名儿童中，由于 ARID1B（富含 AT 相互作用域蛋白 1B）基因突变，出现了原发性（开角）青光眼。在本文中，我们首次报道了 CSS9 合并青光眼，以及首次报道了任何形式的 Coffin-Siris 综合征合并继发性青光眼。这些发现表明，继发性青光眼是 Coffin-Siris 综合征患者的一个偶发表现。
一名患有儿童期青光眼的儿童在德国美因茨的儿童青光眼中心接受了评估和治疗。全身麻醉下的检查显示，前节先天异常（ASD）（Peters 型虹膜角膜发育不良）合并先天性角膜缘干细胞缺乏症（LSCD）、无虹膜和白内障。患者还存在多种其他先天性异常和严重的发育迟缓。为了解释他的畸形组合，于 2018 年底和 2019 年初对患者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 个基因的panel 诊断显示正常结果后，进行了全外显子测序，发现了一个新的可能致病性杂合变异 c.251G>T，p.(Gly84Val)，位于 SOX11 基因（SRY 相关 HMG 盒基因 11）中。该变异是新生的。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，基因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发特征。由于早期治疗可能改善青光眼患者的视力预后，我们建议 Coffin-Siris 综合征患者应接受特定的眼科筛查。
