Clinical features and genetic analysis of West syndrome caused by CLCN6 mutations(report of one case)
10.3969/j.issn.1004-1648.2025.02.018
- VernacularTitle:CLCN6突变引起的West综合征的临床特征及遗传学分析(附1例报告)
- Author:
Qingmei YANG
1
;
Tangfeng SU
;
Liqing CHEN
Author Information
1. 430030 武汉,华中科技大学同济医学院同济医院儿童神经内科
- Publication Type:Journal Article
- Keywords:
CLCN6;
West syndrome;
whole exome sequencing;
missense mutation
- From:
Journal of Clinical Neurology
2025;38(2):130-134
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the clinical features and genetic characteristics of West syndrome(WS)caused by CLCN6 mutations.Methods A case of WS caused by CLCN6 mutations was reported.And the literatures were reviewed.The clinical features and gene mutation characteristics of CLCN6 associated WS were analyzed.Results This patient,a male,presented with symptoms at 7 months of age,and exhibited clinical features including spasms,developmental delay,and high-amplitude disorganized of EEG.At 11 months of age,a combination of topiramate and clonazepam controlled the seizures.By 1-year-old,the EEG normalized,and at 39 months of age,the patient discontinued medication without experiencing further seizures;however,language development remained delayed.Whole exome sequencing identified a de novo missense mutation in CLCN6(c.761T＞C,p.F54S),which was highly conserved.Multiple online prediction tools classified this mutation as deleterious.According to the guidelines of the American college of medical genetics and genomics,this variant was classified as likely pathogenic(PS2+PM2+PP3).A literature review included three cases(including this one).Clinical features included spasms(3/3,with 2 cases evolved into tonic-clonic and myoclonic seizures),intellectual or global developmental delay(3/3),behavioral disorders(1/3),sleep disorders(1/3),visual impairment(1/3),microcephaly(2/3),high-amplitude disorganized of EEG(3/3),and enlarged subarachnoid spaces on head MRI(2/3).After treatment,seizures in one patient were controlled,while two cases developed drug-resistant epilepsy.The CLCN6 mutations reported include c.533A＞C,c.599A＞C,and c.761T＞C,all of which are de novo missense mutations located in the transmembrane domains.Conclusions WS caused by CLCN6 mutations is associated with a poor neurodevelopmental prognosis.The mutations are primarily de novo missense mutations.Early genetic diagnosis is crucial for improving the prognosis.
