Longitudinal Evaluation of Neuromuscular Involvement in Type 1 Myotonic Dystrophy

Primary objective: To determine the sensitivity to change of neuromuscular functional outcomes during the natural (non-interventional) progression of myotonic dystrophy type 1 (DM1), in order to identify the most relevant and robust outcome measures for use in therapeutic trials. Secondary objective: To compare patients with DM1 to healthy control subjects to assess the discriminative power of biomechanical and electrophysiological parameters. Study design: This is an open-label, single-center observational study with no direct individual benefit. Participants: Thirty patients with DM1 will be evaluated three times over a three-year period, while thirty control subjects will be assessed once. Timeline: The planned inclusion period is 12 months, with a follow-up duration of 36 months, resulting in a total study duration of 48 months. Functional assessment-particularly muscle strength-is essential for both diagnosis and longitudinal monitoring of neuromuscular diseases. In therapeutic trials, outcome measures must meet strict scientific requirements, including precision, sensitivity, and reliability. Muscle strength is frequently used as a primary or secondary endpoint in trials targeting neuromuscular disorders. Even modest functional improvements resulting from therapy must be detectable with sensitive measurement tools. Myotonic dystrophy is the most common muscular dystrophy in adults, with an estimated prevalence of 1 in 8,000. It is a genetic disorder inherited in an autosomal dominant manner. Two genetically distinct forms are recognized: myotonic dystrophy type 1 (DM1, or Steinert disease) and the rarer, more recently identified type 2 (DM2). This study focuses on DM1 due to its higher prevalence and greater clinical severity. The study will assess parameters related to myotonia, muscle strength, motor function, and neuromuscular excitability. Patients will be evaluated every 18 months over a three-year period. Control subjects will undergo a single assessment. The expected outcome is the identification of the most robust and sensitive parameters for longitudinal monitoring of DM1 patients, particularly in the context of future therapeutic trials. A similar study will be conducted in parallel in Quebec (Principal Investigator: Prof. Jack Pumirat, CHU de Québec). Data common to both centers will be analyzed jointly.