Longitudinal Evaluation of Disease Progression in Congenital Myotonic Dystrophy

Objective: To determine the longitudinal progression of symptoms in children with congenital myotonic dystrophy (CDM). Background: Congenital myotonic dystrophy (CDM) is the severe, infantile-onset form of myotonic dystrophy. Prior cross-sectional studies identified variable improvement in symptoms with age, in contrast to adults. Design/Methods: Participants with CDM and healthy controls between the ages of 0–13 were enrolled in the study cohorts, stratified by age to ensure an even distribution of ages. Visits occurred over a 2-day period at baseline, 12, and 24 months. Each cohort received an age appropriate clinical evaluation. This includes neuropsychological testing, oral facial strength testing, strength and functional testing, DEXA, ECG, and quality of life measurements. Results: Forty-nine participants with CDM and 29 age matched healthy controls were enrolled. The mean decline over 12 months in the IQ was −7.2%. The mean change in the lip force was 11%, with participants under 10 years of age improving 17.2% and those older than 10 improving 0.8%. On the six minute walk, the mean improvement up to age 10 was 48.9%, then after age 10 it was 4.9%. The mean right grip strength increased 0.42 kgs (SD 1.87), or 7.3%. The total body mass increased 33.7% over 12 months. The PDSS, a measure of daytime sleepiness, improved 3.8% for those participants under 10 years old and declined −44.5% for those participants over age 10. Conclusions: This work supports improvement in some functional measures during childhood, and identifies a potential plateau in strength after the age of 10. These data identify potential clinical outcome assessments for use in therapeutic trials. Study Supported by: The Muscular Dystrophy Association, NINDS (1K23NS091511-01), and Utah Neuromuscular Fund. Disclosure: Dr. Johnson has received personal compensation for consulting, serving on a scientific advisory board, speakering, or other activities with AMO Pharma, AveXis and Strongbridge Pharma. Dr. Johnson has received compensation in an editorial capacity for Neurology Genetics. Dr. Johnson has received research support from Biogen Idec, Cytokinetics, AMO Pharma, AveXis and Ionis Pharmaceuticals. Dr. McIntyre has nothing to disclose. Dr. Dixon has nothing to disclose. Dr. Crockett has nothing to disclose. Dr. Bounsanga has nothing to disclose. Dr. Hung has nothing to disclose. Dr. Campbell has nothing to disclose.