Congenital and childhood myotonic dystrophy: Current aspects of disease and future directions

Abstract

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.

Keywords: Clinical manifestations; Myotonic dystrophy type 1; Childhood myotonic dystrophy; Congenital myotonic dystrophy; Natural history; Management

Core tip: Type 1 myotonic dystrophy is an often undetected neuromuscular disease in paediatric patients with variable clinical manifestations and burden of disease. We review the current understandings of disease pathogenesis, symptoms and management in congenital and childhood myotonic dystrophy with a particular focus on hypersomnolence and sleep disorders. Future directions should target standardised care and regular surveillance, understanding pathophysiology and new treatment strategies.