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Abstract：
BACKGROUND: 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.
METHODS: 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).
CONCLUSIONS: 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.
METHODS: 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).
CONCLUSIONS: 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.
摘要：
背景：严重的先天性眼科畸形和青光眼可能是Coffin-Siris综合征（CSS）患者的重要偶发特征，特别是由SOX11突变引起的Coffin-Siris综合征9（CSS9，OMIM#615866）。最近,原发性（开角型）青光眼在两名儿童中被描述为最常见的Coffin-Siris综合征，CSS1(OMIM#135900)由ARID1B(含AT-富相互作用域的蛋白1B)基因突变。在这篇文章中,我们介绍了青光眼合并Coffin-Siris综合征9的第一份报告,以及继发性青光眼合并任何形式的Coffin-Siris综合征的第一份报告.这些发现表明，在Coffin-Siris综合征患者中，继发性青光眼是偶发的。
方法：在美因茨的儿童青光眼中心对患有继发性儿童青光眼和其他眼部表现的儿童进行了评估和治疗。德国。全身麻醉下的检查显示眼眼前节发育不全（ASD）（Peters型虹膜角膜发育不全）合并先天性角膜缘干细胞缺乏症（LSCD），无虹膜,和白内障。患者还患有多种其他先天性异常和严重的发育迟缓。为了解释他的异常组合，我们在2018年末和2019年初进行了外周血分子遗传学分析.根据与先天性青光眼相关的18个基因的小组诊断结果，进行了全外显子组测序，发现了一个新的可能的致病性杂合变体c.251G>T，p.(Gly84Val)在SOX11基因(SRY相关的HMG-box基因11)中。该变体从头发生。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).
结论：当眼部疾病与其他系统特征同时发生时，遗传分析可能是开创性的。结果表明，青光眼是Coffin-Siris综合征患者的偶发特征。早期治疗可以改善青光眼患者的视力，我们建议Coffin-Siris综合征患者应接受特定的眼科筛查.
方法：在美因茨的儿童青光眼中心对患有继发性儿童青光眼和其他眼部表现的儿童进行了评估和治疗。德国。全身麻醉下的检查显示眼眼前节发育不全（ASD）（Peters型虹膜角膜发育不全）合并先天性角膜缘干细胞缺乏症（LSCD），无虹膜,和白内障。患者还患有多种其他先天性异常和严重的发育迟缓。为了解释他的异常组合，我们在2018年末和2019年初进行了外周血分子遗传学分析.根据与先天性青光眼相关的18个基因的小组诊断结果，进行了全外显子组测序，发现了一个新的可能的致病性杂合变体c.251G>T，p.(Gly84Val)在SOX11基因(SRY相关的HMG-box基因11)中。该变体从头发生。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).
结论：当眼部疾病与其他系统特征同时发生时，遗传分析可能是开创性的。结果表明，青光眼是Coffin-Siris综合征患者的偶发特征。早期治疗可以改善青光眼患者的视力，我们建议Coffin-Siris综合征患者应接受特定的眼科筛查.
