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Abstract：
Slow-channel congenital myasthenic syndrome (CMS) is a rare subtype of CMS caused by dominant \"gain of function\" mutations in the acetylcholine receptor. Clinically, the cervical and forearm extensor muscles seem to be preferentially weaker; and conventional treatment with anticholinesterases fails to improve symptoms. In contrast, open channel blockers such as fluoxetine and quinidine have been shown to be of benefit. The objectives of our study were to provide further insight into the clinical features of slow-channel CMS and evaluate response to recommended therapy. We carried out a retrospective clinical follow up study of 15 slow-channel CMS patients referred to the Munich CMS Centre. Detailed clinical data were collected by clinicians involved in the care of each patient, with a particular focus on response and tolerability to recommended therapy. Patients varied widely as regard onset of symptoms, severity of disease and mutations involved. Patients received up to four different medications and some had none. Our results strengthen previous reported findings in terms of clinical phenotype variability and the poor response to pyridostigmine. Although treatment with fluoxetine was beneficial in most patients, a number of our patients suffered significant adverse effects that hindered optimum dose titration or led to treatment cessation. Slow-channel CMS is rare and exhibits distinct clinical and genetic characteristics. Our study suggests that fluoxetine, despite being effective in most patients, can be associated with significant side effects, thus reducing treatment effectiveness in clinical practice.
摘要：
慢通道先天性肌无力综合征（CMS）是一种罕见的CMS亚型，由乙酰胆碱受体的显性“功能获得”突变引起。临床上,颈椎和前臂伸肌似乎优先较弱；常规抗胆碱酯酶治疗不能改善症状。相比之下,开放通道阻滞剂如氟西汀和奎尼丁已被证明是有益的。我们研究的目的是进一步了解慢通道CMS的临床特征并评估对推荐治疗的反应。我们对转诊到慕尼黑CMS中心的15名慢通道CMS患者进行了回顾性临床随访研究。详细的临床数据由参与护理每位患者的临床医生收集，特别关注对推荐治疗的反应和耐受性。患者在症状发作方面差异很大，疾病的严重程度和涉及的突变。患者接受了多达四种不同的药物，有些则没有。我们的结果在临床表型变异性和对吡啶斯的明的不良反应方面加强了先前报道的发现。尽管氟西汀治疗对大多数患者有益，我们的一些患者出现了严重的不良反应,这些不良反应阻碍了最佳剂量的调整或导致治疗停止.慢通道CMS很少见，并具有明显的临床和遗传特征。我们的研究表明氟西汀,尽管对大多数患者有效，可能与显著的副作用有关，从而降低了临床实践中的治疗效果。
