Disease Burden and Functional Outcomes in Congenital Myotonic Dystrophy: A Cross-Sectional Study (S43.008)

Abstract

OBJECTIVE: To describe a profile of congenital myotonic dystrophy throughout childhood and identify appropriate clinical endpoints for future therapeutic trials. BACKGROUND: Congenital myotonic dystrophy (CDM) is a severe, infantile-onset form of myotonic dystrophy (DM1). There have been few clinical studies evaluating the natural history of CDM during childhood. DESIGN/METHODS: Patients with CDM between 0-13 years of age were enrolled in this study. Patients and age matched controls were divided into age-based cohorts (0-2, 3-6, and 7-13 years). Each cohort received a 2-day clinical evaluation including: neuropsychological testing, oral facial strength, motor strength and function, DEXA, ECG, and measurements of quality-of-life and disease burden. Subjects were evaluated over a two-day period. All statistical analyses were pairwise comparisons with a p-value less than 0.001 reported as significant. RESULTS: We recruited 41 subjects with CDM and 29 control subjects were recruited. In CDM patients, the mean IQ (65.8; SD 18.4) was three standard deviations below the mean compared to standardized norms. For oral facial strength, the mean lip force strength was significantly different in CDM patients (2.1 Newtons (SD 2.8)) compared to control subjects (17.8 Newtons (SD 7.6)). The six-minute walk was significantly different between CDM subjects (258.3 meters (SD 176.0)) and control subjects (568.2 meters (SD 73.2)). Measurements of grip strength, sleep quality, and quality-of-life were also significantly different. Right arm lean body mass correlated with measures of grip (r=.91) and pinch (r=0.82), while right leg lean body mass correlated with the 6MWT (r=0.62). Strength measures (oral facial strength, grip strength, and 6-minute walk) correlated with each other but not with participant IQ. CONCLUSIONS: This work comprehensively identifies the changes associated with CDM during childhood. Several measures were significantly different between CDM and control subjects and may be useful during future therapeutic trials. Study support: NINDS (1K23NS091511-01) and The Muscular Dystrophy Association

Disclosure: Dr. Johnson has received research support from Biogen Idec and ISIS Pharmaceuticals. Dr. Hung has nothing to disclose. Dr. Dixon has nothing to disclose. Dr. DiBella has nothing to disclose. Dr. Pucillo has nothing to disclose. Dr. Berggren has nothing to disclose. Dr. Hayes has nothing to disclose. Dr. Chen has nothing to disclose. Dr. Butterfield has nothing to disclose. Dr. Heatwole has nothing to disclose. Dr. Campbell has nothing to disclose.