Department of Child, Adolescent and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Slovenia.
Department of Child, Adolescent and Developmental Neurology, University Children's Hospital, University Medical Centre Ljubljana, Slovenia; Faculty of Medicine, University of Ljubljana, Slovenia.
Eur J Paediatr Neurol. 2020 May;26:34-38. doi: 10.1016/j.ejpn.2020.02.002. Epub 2020 Feb 11.
Congenital myasthenic syndromes (CMS) are rare, genetically and phenotypically diverse disorders of neuromuscular transmission. Data on prevalence among children are scarce. Whole exome sequencing facilitated discovery of novel CMS mutations and enabled targeted treatment. Our aim was to identify the prevalence, genetic subtypes and clinical characteristics of CMS in pediatric population of Slovenia.
In this observational, national, cross-sectional study, medical records were retrospectively reviewed. Children with genetically confirmed CMS, referred over a 19 - year period (2000-2018) to the University Medical Centre, Ljubljana, Slovenia, were included in the study. Genetic and phenotypic characteristics were collected and prevalence of CMS in children was calculated.
Eight children with a confirmed genetic mutation in 5 different genes (CHRNE, CHRND, RAPSN, CHAT, MUSK) causative of the CMS were identified. Calculated prevalence of genetically confirmed CMS was 22.2 cases per 1.000.000 children at the end of 2018.
The prevalence of genetically confirmed CMS in Slovenian children at the end of 2018 exceeds previously reported prevalence by more than two-fold, which suggests that prevalence in the literature is likely to be underestimated. Two extremely rarely detected mutations in MUSK and CHRND gene were detected and patient's clinical descriptions add important information on genotype-phenotype correlation.
先天性肌无力综合征（CMS）是一种罕见的、具有遗传和表型多样性的神经肌肉传递障碍。儿童患病率的数据稀缺。全外显子组测序有助于发现新的 CMS 突变，并实现靶向治疗。我们的目的是确定斯洛文尼亚儿科人群中 CMS 的患病率、遗传亚型和临床特征。
在这项观察性、全国性、横断面研究中，回顾性审查了病历。将 19 年来（2000-2018 年）转诊到斯洛文尼亚卢布尔雅那大学医学中心的经基因证实的 CMS 儿童纳入研究。收集了遗传和表型特征，并计算了 CMS 在儿童中的患病率。
确定了 8 名儿童存在 5 种不同基因（CHRNE、CHRND、RAPSN、CHAT、MUSK）的基因突变，导致 CMS。截至 2018 年底，基因确诊 CMS 的患病率为每 100 万儿童 22.2 例。
截至 2018 年底，斯洛文尼亚儿童中基因确诊 CMS 的患病率超过了之前报告的患病率两倍多，这表明文献中的患病率可能被低估了。在 MUSK 和 CHRND 基因中检测到了两种极为罕见的突变，患者的临床描述提供了关于基因型-表型相关性的重要信息。
