Myotonic dystrophies (DMs) are pleotropic multisystemic diseases. These dominantly transmitted repeat disorders affect multiple organs of the human body at all ages – from the newborns to the elderly. DMs are highly inconsistent in terms of age at onset, severity of symptoms, and clinical patterns. Even within families, the onset and pattern of organ involvement remains enigmatic. Anticipation, with aggravation of the disease severity and earlier age at onset through successive generations, is particularly evident in DM1 that can affect adults and children at birth (congenital DM1, CDM) or during childhood. 25 years ago, the identification of the DM1 repeat mutation in the DMPK gene on chromosome 19 opened the box for these diseases. The highly unstable CTG repeat expansion involved in DM1 usually increases from one generation to the next and is, to some extent, linked to disease severity. Clinically, patients with DM1 can be subdivided into five main classes, distinguishable by the prevalence of the presenting clinical pattern: congenital, childhood-onset, juvenile, adult-onset, and late-onset/asymptomatic. In myotonic dystrophy type 1 (DM1), the disease leads to a premature death, whereas in myotonic dystrophy type 2 (DM2) premature aging can be observed. In the past decades, much progress has been made in the molecular understanding of the underlying DNA and RNA mechanisms of clinical miscellaneous DM symptoms. We are presently on the verge of transferring multiple bench-made molecular experimental therapies and knowledge into clinical therapeutic tools and reality, with the ultimate aim of alleviating and, eventually, curing the diseases.
This collection of original contributions and standpoint reviews from multiple leading DM centres in Europe describes the state of the art for the characterization of the DM diseases, the development of molecular strategies to target its multisystemic nature, and provides evidence of screening and testing novel therapeutic avenues.
Myotonic dystrophies (DMs) are pleotropic multisystemic diseases. These dominantly transmitted repeat disorders affect multiple organs of the human body at all ages – from the newborns to the elderly. DMs are highly inconsistent in terms of age at onset, severity of symptoms, and clinical patterns. Even within families, the onset and pattern of organ involvement remains enigmatic. Anticipation, with aggravation of the disease severity and earlier age at onset through successive generations, is particularly evident in DM1 that can affect adults and children at birth (congenital DM1, CDM) or during childhood. 25 years ago, the identification of the DM1 repeat mutation in the DMPK gene on chromosome 19 opened the box for these diseases. The highly unstable CTG repeat expansion involved in DM1 usually increases from one generation to the next and is, to some extent, linked to disease severity. Clinically, patients with DM1 can be subdivided into five main classes, distinguishable by the prevalence of the presenting clinical pattern: congenital, childhood-onset, juvenile, adult-onset, and late-onset/asymptomatic. In myotonic dystrophy type 1 (DM1), the disease leads to a premature death, whereas in myotonic dystrophy type 2 (DM2) premature aging can be observed. In the past decades, much progress has been made in the molecular understanding of the underlying DNA and RNA mechanisms of clinical miscellaneous DM symptoms. We are presently on the verge of transferring multiple bench-made molecular experimental therapies and knowledge into clinical therapeutic tools and reality, with the ultimate aim of alleviating and, eventually, curing the diseases.
This collection of original contributions and standpoint reviews from multiple leading DM centres in Europe describes the state of the art for the characterization of the DM diseases, the development of molecular strategies to target its multisystemic nature, and provides evidence of screening and testing novel therapeutic avenues.