Congenital myasthenic syndromes (CMS) are a group of inherited disorders caused by mutations in genes encoding proteins essential for neuromuscular transmission. CMS is characterized by fatigable muscle weakness with onset at birth or in early childhood; rarely, symptoms may present later. The most frequently involved proteins are choline acetyltransferase, the endplate species of acetylcholinesterase and the acetylcholine receptor subunits. Defects in the cholinergic receptor nicotinic delta subunit (CHRND) are a rare cause for CMS but they should be considered in patients with a severe, early onset disease, with respiratory distress. We describe two sisters, clinically and genetically diagnosed with CMS, carrying two heteroallelic variants in the CHRND gene: c.730C>T; p.(Arg244Cys) and c.1304T>C; p.(Leu435Pro). The first variant has already been described yet no clinical relevance has been proved; the second one, is a novel variant documented here for the first time. These two cases expand the clinical spectrum of CMS linked to CHRND mutations.

中文翻译：

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与 CHRND 基因的新型双等位基因突变相关的严重先天性肌无力综合征

先天性肌无力综合征 (CMS) 是一组遗传性疾病，由编码神经肌肉传递必需蛋白质的基因突变引起。CMS 的特点是在出生时或儿童早期就出现易疲劳的肌肉无力；极少数情况下，症状可能会在以后出现。最常涉及的蛋白质是胆碱乙酰转移酶、乙酰胆碱酯酶的终板种类和乙酰胆碱受体亚基。胆碱能受体烟碱 δ 亚基 (CHRND) 的缺陷是 CMS 的罕见原因，但在患有严重的早发疾病并伴有呼吸窘迫的患者中应考虑这些缺陷。我们描述了两个在临床和基因上被诊断为 CMS 的姐妹，在 CHRND 基因中携带两个异等位基因变异：c.730C>T；p.(Arg244Cys) 和 c.1304T>C；p.(Leu435Pro)。已经描述了第一个变体，但尚未证明临床相关性；第二个，是第一次在这里记录的新变种。这两个案例扩大了与 CHRND 突变相关的 CMS 的临床范围。