Echenne Bernard, Bassez Guillaume
Neuromuscular Illness Reference Center, Pediatric Neurology Service, Hôpital Gui de Chauliac, Université de Montpellier I, Montpellier, France and Sherbrooke University, Sherbrooke,Canada.
Handb Clin Neurol. 2013;113:1387-93. doi: 10.1016/B978-0-444-59565-2.00009-5.
Myotonic dystrophy (DM) encompasses two gene defects, DM1 (myotonic dystrophy type 1) being currently the sole disorder leading to a childhood form of the disease. As consequence of the non coding unstable CTG repeat expansion mutation, DM1 presents as an extremely wide and diverse clinical continuum ranging from antenatal to late adult forms, the complexity of the disease being reinforced by multisystemic involvement. The congenital form appears as the most severe end of the phenotypic spectrum and may include marked neonatal hypotonia, respiratory failure, facial diplegia, contractures, and mental retardation. Brain involvement is the hallmark of childhood-onset DM1, distinguished by a normal neonatal period, with learning difficulties as the main presenting symptom, resulting from various degrees of mental delay, psychopathological manifestations, speech defects, hypersomnolence, and fatigue. In contrast, muscle weakness remains usually moderate in childhood, limited to facial weakness, ptosis, and dysarthria, until a decline from the second decade. Orthopedic manifestations including kyphoscoliosis and equinovarus may require surgery. Other organs involvement includes frequent abdominal symptoms, whereas endocrine disturbance is rare. Symptomatic cardiac arrhythmia, mainly exercise-induced, can be observed. While current treatment is mainly symptomatic, future clinical trials are expected following significant progress in pathophysiology and the recent development of molecular therapy approaches.
强直性肌营养不良(DM)包含两种基因缺陷,其中DM1(1型强直性肌营养不良)是目前导致儿童期该疾病的唯一病症。由于非编码不稳定CTG重复序列扩增突变,DM1呈现出从产前到成年晚期极为广泛且多样的临床连续谱,多系统受累加剧了该疾病的复杂性。先天性形式表现为表型谱中最严重的一端,可能包括显著的新生儿肌张力减退、呼吸衰竭、双侧面瘫、挛缩和智力发育迟缓。脑部受累是儿童期发病的DM1的标志,其特点是新生儿期正常,主要表现症状为学习困难,这是由不同程度的智力发育迟缓、精神病理表现、言语缺陷、嗜睡和疲劳导致的。相比之下,儿童期肌肉无力通常较轻,仅限于面部无力、上睑下垂和构音障碍,直到第二个十年开始病情恶化。包括脊柱侧弯和马蹄内翻足在内的骨科表现可能需要手术治疗。其他器官受累包括频繁出现腹部症状,而内分泌紊乱则较为罕见。可观察到有症状性心律失常,主要由运动诱发。虽然目前的治疗主要是对症治疗,但随着病理生理学取得重大进展以及分子治疗方法的最新发展,预计未来会开展临床试验。