Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions.
Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions.
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DOI：
10.5409/wjcp.v4.i4.66
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发表时间：
2015-11-08
期刊：
影响因子：
--
通讯作者：
Farrar, Michelle
中科院分区：
文献类型：
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作者：
Ho, Genevieve;Cardamone, Michael;Farrar, Michelle
肌强直性营养不良1型（DM1）是由肌强直性蛋白激酶基因非翻译区CTG突变扩增引起的多系统疾病。虽然DM1是最常见的成人肌肉萎缩症，全球患病率为八分之一，但发病年龄从出生前到成年期各不相同。临床严重程度的范围很广，从轻微到严重，这与DNA重复次数有关。重要的是，先天性和儿童期DM1的早期临床表现和处理不同于典型的成人DM1。在新生儿和儿童中，DM1主要影响肌肉力量、认知、呼吸、中枢神经和胃肠道系统。睡眠障碍通常没有得到充分认识，但却是一种重要的发病率。目前还没有有效的疾病改善治疗方法，患有DM1的新生儿和儿童可能会出现严重的身体和智力残疾，在最严重的情况下可能会限制生命。目前的管理是支持性的，包括定期监测和治疗症状。针对异常剪接的基因和致病机制的新疗法正在出现。遗传咨询对于这种常染色体显性遗传病至关重要，它具有不同的外显率和潜在的产妇预产期，同时也有助于计划生育和开展级联检测，以便在受影响的家庭成员中开展健康监测。本文综述了先天性和儿童期DM1的临床表现和治疗，特别关注嗜睡和睡眠障碍。此外，本文还将对DM1的分子遗传学、发病机制和新治疗策略的发展进行综述。
Myotonic dystrophy type 1 (DM1) is multisystem disease arising from mutant CTG expansion in the non-translating region of the dystrophia myotonica protein kinase gene. While DM1 is the most common adult muscular dystrophy, with a worldwide prevalence of one in eight thousand, age of onset varies from before birth to adulthood. There is a broad spectrum of clinical severity, ranging from mild to severe, which correlates with number of DNA repeats. Importantly, the early clinical manifestations and management in congenital and childhood DM1 differ from classic adult DM1. In neonates and children, DM1 predominantly affects muscle strength, cognition, respiratory, central nervous and gastrointestinal systems. Sleep disorders are often under recognised yet a significant morbidity. No effective disease modifying treatment is currently available and neonates and children with DM1 may experience severe physical and intellectual disability, which may be life limiting in the most severe forms. Management is currently supportive, incorporating regular surveillance and treatment of manifestations. Novel therapies, which target the gene and the pathogenic mechanism of abnormal splicing are emerging. Genetic counselling is critical in this autosomal dominant genetic disease with variable penetrance and potential maternal anticipation, as is assisting with family planning and undertaking cascade testing to instigate health surveillance in affected family members. This review incorporates discussion of the clinical manifestations and management of congenital and childhood DM1, with a particular focus on hypersomnolence and sleep disorders. In addition, the molecular genetics, mechanisms of disease pathogenesis and development of novel treatment strategies in DM1 will be summarised.