PDF(Pubmed)
Abstract：
Congenital myasthenic syndrome with episodic apnea is associated with pathogenic variants in the CHAT gene. While respiratory disorders and oculomotor findings are commonly reported in affected individuals, a subset of patients only present with muscle weakness and/or ptosis but not apneic crises. In this case series, we describe five individuals with exercise intolerance caused by single nucleotide variants in the CHAT gene. The age of onset ranged from 1 to 2.5 years, and all patients exhibited a fluctuating course of congenital myasthenic syndrome without disease progression over several years. Notably, these patients maintained a normal neurological status, except for the presence of abnormal fatigability in their leg muscles following prolonged physical activity. We conducted a modified protocol of repetitive nerve stimulation on the peroneal nerve, revealing an increased decrement in amplitude and area of compound muscle action potentials of the tibialis anterior muscle after 15-20 min of exercise. Treatment with 3,4-diaminopyridine showed clear improvement in two children, while one patient experienced severe adverse effects and is currently receiving a combination of Salbutamol Syrup and pyridostigmine with slight positive effects. Based on our findings and previous cases of early childhood onset with muscle fatigability as the sole manifestation, we propose the existence of a mild phenotype characterized by the absence of apneic episodes.
摘要：
伴有发作性呼吸暂停的先天性肌无力综合征与CHAT基因的致病变异有关.虽然呼吸系统疾病和动眼表现通常在受影响的个体中报道，一部分患者仅出现肌肉无力和/或上睑下垂，但未出现呼吸暂停危象。在这个系列中,我们描述了5例CHAT基因单核苷酸变异导致的运动不耐受患者.发病年龄1~2.5岁,所有患者都表现出先天性肌无力综合征的波动过程，几年来没有疾病进展。值得注意的是,这些患者维持正常的神经状态，除了长期体力活动后腿部肌肉存在异常疲劳。我们对腓骨神经进行了重复神经刺激的改良方案，运动15-20分钟后，胫骨前肌的复合肌肉动作电位的幅度和面积增加。用3,4-二氨基吡啶治疗在两名儿童中显示出明显的改善，而一名患者出现了严重的不良反应，目前正在接受沙丁胺醇糖浆和吡啶斯的明的联合治疗，效果轻微。根据我们的发现和以前的儿童早期发病以肌肉疲劳为唯一表现的病例，我们提出存在一种轻度表型，其特征是没有呼吸暂停发作。
