Kaminsky P, Pruna L
Service de médecine interne orientée vers les maladies orphelines et systémiques, pôle des spécialités médicales, centre de référence des maladies neuromusculaires de Nancy, centre hospitalier universitaire de Nancy, hôpitaux de Brabois, rue du Morvan, 54511 Vandœuvre cedex, France.
Rev Med Interne. 2012 Sep;33(9):514-8. doi: 10.1016/j.revmed.2012.03.355. Epub 2012 May 8.
Type 1 myotonic dystrophy is an autosomal dominant inherited disorder related to the expansion of a trinucleotide (CTG) repeat in the exon 15 in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Mutant transcripts containing an expanded CUG repeat are retained in nuclear foci and cause numerous dysfunctions by interfering with biogenesis of other mRNAs. Prominent clinical features are progressive muscular weakness and myotonia, which affect skeletal muscles but also white muscles leading to digestive, urinary and obstetrical disorders. Functional prognosis correlates with motor handicap and vital prognosis is linked to cardiac rhythm disturbances and conduction defects due to progressive subendocardial fibrosis, and to complex respiratory dysfunctions, which associate restrictive lung disease, involvement of the central inspiratory pathway, and sleep apnea. Other clinical features are lens opacity, glucose intolerance, metabolic syndrome, several endocrine disorders (gonadal deficiency, hyperparathydoidism), or immunoglobulin deficiency due to immunoglobulin G hypercatabolism. Life expectancy is reduced in myotonic dystrophy, and death is mainly caused by respiratory complications, but also by cardiac arrhythmias. Moreover, an abnormal incidence of tumors has been reported. Therefore, myotonic dystrophy does not only concern neurologists but a multidisciplinary approach is necessary, including at least pneumologist, cardiologist, and physiotherapist. General internists should also be implicated, not only in the initial diagnosis step, but also in the diagnosis of complications and their treatments.
1型强直性肌营养不良是一种常染色体显性遗传性疾病，与强直性肌营养不良蛋白激酶（DMPK）基因3'非翻译区外显子15中的三核苷酸（CTG）重复序列扩增有关。含有扩增CUG重复序列的突变转录本保留在核仁中，并通过干扰其他mRNA的生物合成导致多种功能障碍。突出的临床特征是进行性肌无力和肌强直，其不仅影响骨骼肌，还影响白肌，导致消化、泌尿和产科疾病。功能预后与运动障碍相关，而生命预后与进行性心内膜下纤维化导致的心律失常和传导缺陷以及复杂的呼吸功能障碍有关，后者伴有限制性肺病、中枢吸气途径受累和睡眠呼吸暂停。其他临床特征包括晶状体混浊、葡萄糖不耐受、代谢综合征、多种内分泌疾病（性腺功能减退、甲状旁腺功能亢进）或由于免疫球蛋白G高分解代谢导致的免疫球蛋白缺乏。强直性肌营养不良患者的预期寿命缩短，死亡主要由呼吸并发症引起，但也可由心律失常导致。此外，还报道了肿瘤的异常发病率。因此，强直性肌营养不良不仅涉及神经科医生，还需要多学科方法，至少包括呼吸科医生、心脏病专家和物理治疗师。普通内科医生也应参与其中，不仅在初始诊断阶段，还包括并发症的诊断及其治疗。
