Abstract Aim 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. Methods 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. Results 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. Interpretation 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.

中文翻译：

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斯洛文尼亚儿童先天性肌无力综合征的患病率和遗传亚型

摘要 目的 先天性肌无力综合征 (CMS) 是罕见的、遗传和表型多样的神经肌肉传递疾病。关于儿童患病率的数据很少。全外显子组测序促进了新的 CMS 突变的发现并实现了靶向治疗。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。方法 在这项观察性、全国性、横断面研究中，对医疗记录进行了回顾性审查。该研究包括在 19 年期间（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。收集遗传和表型特征并计算儿童 CMS 的患病率。结果 鉴定出 8 名儿童，其 5 个不同基因（CHRNE、CHRND、RAPSN、CHAT、MUSK）的基因突变导致 CMS。2018 年底，经基因证实的 CMS 的计算患病率为每 1.000.000 名儿童 22.2 例。 解释 2018 年底，斯洛文尼亚儿童中经基因证实的 CMS 的患病率是先前报告的患病率的两倍以上，这表明患病率在文献中很可能被低估了。在 MUSK 和 CHRND 基因中检测到两个极少检测到的突变，患者的临床描述增加了有关基因型-表型相关性的重要信息。2018 年底有 000 名儿童。 解读 2018 年底斯洛文尼亚儿童基因确诊 CMS 的患病率是先前报道的患病率的两倍以上，这表明文献中的患病率可能被低估了。在 MUSK 和 CHRND 基因中检测到两个极少检测到的突变，患者的临床描述增加了有关基因型-表型相关性的重要信息。2018 年底有 000 名儿童。 解读 2018 年底斯洛文尼亚儿童基因确诊 CMS 的患病率是先前报道的患病率的两倍以上，这表明文献中的患病率可能被低估了。在 MUSK 和 CHRND 基因中检测到两个极少检测到的突变，患者的临床描述增加了有关基因型-表型相关性的重要信息。