Myotonic Dystrophy.

Objective: This article reviews the genetic basis, pathogenic mechanisms, epidemiology, clinical presentation, multiorgan involvement, and multidisciplinary management of myotonic dystrophy type 1 (DM1) and type 2 (DM2), as well as the differential diagnosis of myotonic disorders (DM versus nondystrophic myotonic disorders) and electrical myotonia.

Latest developments: Due to underdiagnosis, the prevalence of DM is likely higher than currently recognized. Patients with late-onset or mild phenotypes with little or no skeletal muscle involvement may never be evaluated by a neurologist and thus never diagnosed. Still, DM1 is the most common muscular dystrophy in adults. Scientific progress in understanding the pathogenic mechanism of DM and its broad and variable phenotype has facilitated the design of gene therapy clinical trials in DM1. Nucleic acid-based therapies that target expanded DNA or RNA are in early-stage clinical development. Although caused by a different genetic variation, DM2 shares a common pathogenic mechanism with DM1, which is hopeful for a cure for both subtypes.

Essential points: Neurologists and other clinicians need to recognize DM to ensure prompt diagnosis, effective symptom management, and prevention of life-threatening events. Life-threatening events (eg, sudden death) may occur at any time in the disease course and not necessarily in patients with more severe phenotypes. Investigational drugs may have the potential to have a greater disease-modifying effect when initiated in the early or mild stages of disease, rather than in advanced stages where the therapeutic window may have been missed.