Eymard B, Stojkovic T, Sternberg D, Richard P, Nicole S, Fournier E, Béhin A, Laforêt P, Servais L, Romero N, Fardeau M, Hantaï D
Centre de référence des affections neuromusculaires Paris-Est, service de Neurologie 2, Institut de Myologie, Hôpital de la Pitié-Salpêtrière, 47 bd de l'Hôpital, 75013 Paris, France.
Rev Neurol (Paris). 2013 Feb;169 Suppl 1:S45-55. doi: 10.1016/S0035-3787(13)70060-2.
Congenital myasthenic syndromes (CMS) are a heterogeneous group of disorders caused by genetic defects affecting neuromuscular transmission and leading to muscle weakness accentuated by exertion. Three different aspects have been investigated by members of the national French CMS Network: the difficulties in making a proper diagnosis; the course and long-term prognosis; and the response to therapy, especially for CMS that do not respond to cholinesterase inhibitors. CMS diagnosis is late in most cases because of confusion with other entities such as: congenital myopathies, due to the frequent presentation in patients of myopathies such as permanent muscle weakness, atrophy and scoliosis, and the abnormalities of internal structure, diameter and distribution of fibers (type I predominance, type II atrophy) seen on biopsy; seronegative autoimmune myasthenia gravis, when CMS is of late onset; and metabolic myopathy, with the presence of lipidosis in muscle. The long-term prognosis of CMS was studied in a series of 79 patients recruited with the following gene mutations: CHRNA; CHRNE; DOK7; COLQ; RAPSN; AGRN; and MUSK. Disease-course patterns (progressive worsening, exacerbation, stability, improvement) could be variable throughout life in a given patient. DOK7 patients had the most severe disease course with progressive worsening: of the eight wheelchair-bound and ventilated patients, six had mutations of this gene. Pregnancy was a frequent cause of exacerbation. Anticholinesterase agents are the first-line therapy for CMS patients, except for cases of slow-channel CMS, COLQ and DOK7. In our experience, 3,4-DAP was a useful complement for several patients harboring CMS with AChR loss or RAPSN gene mutations. Ephedrine was given to 18 patients (eight DOK7, five COLQ, four AGRN and one RAPSN). Tolerability was good. Therapeutic responses were encouraging even in the most severely affected patients, particularly with DOK7 and COLQ. Salbutamol was a good alternative in one patient who was allergic to ephedrine.
先天性肌无力综合征（CMS）是一组由影响神经肌肉传递的基因缺陷引起的异质性疾病，劳累会加重肌无力症状。法国全国CMS网络的成员研究了三个不同方面：准确诊断的困难；病程及长期预后；以及对治疗的反应，尤其是对胆碱酯酶抑制剂无反应的CMS。大多数情况下，CMS诊断较晚，原因是与其他疾病混淆，如：先天性肌病，因为患者常表现出肌病症状，如永久性肌无力、萎缩和脊柱侧弯，以及活检时可见的纤维内部结构、直径和分布异常（I型优势、II型萎缩）；血清阴性自身免疫性重症肌无力，当CMS起病较晚时；以及代谢性肌病，伴有肌肉脂质沉积。对79例携带以下基因突变的患者进行了研究：CHRNA；CHRNE；DOK7；COLQ；RAPSN；AGRN；和MUSK。在特定患者的一生中，疾病进程模式（进行性恶化、加重、稳定、改善）可能会有所不同。DOK7患者的病程最为严重，呈进行性恶化：在8例需要轮椅辅助和通气的患者中，有6例携带该基因突变。妊娠是病情加重的常见原因。抗胆碱酯酶药物是CMS患者的一线治疗药物，但慢通道CMS、COLQ和DOK7患者除外。根据我们的经验，3,4 -二氨基吡啶对一些携带AChR缺失或RAPSN基因突变的CMS患者是一种有用的补充治疗。18例患者使用了麻黄碱（8例DOK7、5例COLQ、4例AGRN和1例RAPSN）。耐受性良好。即使是病情最严重的患者，治疗反应也令人鼓舞，尤其是DOK7和COLQ患者。沙丁胺醇是1例对麻黄碱过敏患者的良好替代药物。
