• Change in ambulation over 24 months as measured by the 10 meter walk (m/s). [ Time Frame: 12 and 24 months ]
  10 meter walk will be measured (m/s)
• Change in respiratory function over 24 months as measured by spirometry, specifically the supine forced vital capacity (FVC). [ Time Frame: 12 and 24 months ]
  Supine forced vital capacity (% predicted)
• Percent splicing of DM1-affected splice events [ Time Frame: 3 months ]
  RNA sequenced of muscle biopsy samples collected at two different times will be combined and used to calculate a percent splicing index (PMI)

DM1 has a prevalence rate of approximately 1 per 2,300. There are no expected gender differences. Both men and women will be selected for this study.

Children with DM1 are not included in this project because the pathophysiological basis of congenital and childhood DM1 appears to be mechanistically distinct.

Inclusion criteria:

• Age 18 to 70 (inclusive)
• Competent to provide informed consent
• Clinical diagnosis of DM1 based on research criteria1 or positive genetic test
• Comment: The clinical research criteria require myotonia, muscle weakness in a characteristic distribution, and history of similar findings in a first degree relative. Genetic testing confirmed the diagnosis of DM1 in > 99% of individuals who satisfied these criteria.2

Exclusion criteria:

• Symptomatic renal or liver disease, uncontrolled diabetes or thyroid disorder, or active malignancy other than skin cancer.
• Current alcohol or substance abuse
• Concurrent enrollment in clinical trial for DM1, or participation in trial within 6 months of entry.
• Concurrent pregnancy or planned pregnancy during the course of the study.
• Concurrent medical condition that would, in the opinion of the investigator or clinical evaluator, compromise performance on study measures.
• Note: non-ambulatory participants are not excluded, but are limited to <15% of enrollment.

Inclusion criteria for participants in the muscle biopsy sub-study:

• Of the 95 patients undergoing the tibialis anterior muscle biopsy, at least half will have at least moderate weakness of ankle dorsiflexion, defined as MRC score ≤ 4+. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy. Approximately 10 patients at each site will undergo the muscle biopsy.

Exclusion criteria for 95 participants in the muscle biopsy sub-study:

• Known CTG repeat expansion size less than 100 repeats, unless there are clear cut signs of limb weakness and muscle wasting. This is in order to obtain a muscle tissue sample in a person more severely affected with myotonic dystrophy.
• Use of anticoagulant such as warfarin or a direct oral anticoagulant (e.g. dabigatran) due to the increased risk of bleeding.
• Use of aspirin or non-steroidal anti-inflammatory agents should be discontinued 3 days prior to the biopsy procedure, if possible.
• Platelet count <50,000 (if known) due to the increased risk of bleeding.
• History of a bleeding disorder due to the increased risk of bleeding.
• Advanced wasting of tibialis anterior (TA) muscle that precludes needle muscle biopsy in order to ensure that a sample taken would be of muscle and not just fat and fascia.
• Previous muscle biopsy of either TA in order to provide muscle tissue samples of non-biopsied muscles.

• University of Rochester
• The Methodist Hospital System
• University of Kansas
• Stanford University
• Ohio State University
• National Institutes of Health (NIH)
• University of Florida
• University of Iowa
• University of California, Los Angeles
• Insitut de Myologie Paris
• Ludwig-Maximillians University, Munich
• NEMO Clinic, Milan
• University College, London
• Radboud University