Congenital muscular dystrophies

Identification and development of accurate clinical outcome measures for congenital muscular dystrophies (CMDs) are essential for monitoring disease progression and clinical trial readiness. We present results of a longitudinal study of motor outcome measures in children with two types of CMD, COL6-related dystrophies (COL6-RDs) and LAMA2-related dystrophy (LAMA2-RD). Over the course of four years 48 individuals (24 COL6-RDs and 24 LAMA2-RD) ages 4-22 years were evaluated (22 in year 1; 32 in year 2; 38 in year 3 and 4; 36 in year 5). Assessments included the motor function measure 32 (MFM32), myometry (knee flexors and extensors, elbow flexors and extensors) and goniometry (knee and elbow extension). Separate linear mixed effects models were fit for each outcome measurement, with subject-specific random intercepts. Statistically significant results of the two group analyses based on CMD subtypes are presented here: total MFM scores for COL6-RDs and LAMA2-RD decreased at a rate of 4.36 and 2.93 points respectively each year; all muscle groups for individuals with COL6-RDs decreased between 0.96 and 2.55 percentage points; range of motion measurements of elbow decreased by 3.31 degrees each year in individuals with LAMA2-RD, with a loss of right knee extension range by 2.45 degrees each year in individuals with COL6-RDs. Further analyses of total MFM by ambulatory status showed significant decreases over time in all groups except for ambulatory individuals with LAMA2-RD. Loss of strength as measured by myometry was also evident in all 4 subgroups. Range of motion changes were noted only in the non-ambulant individuals with COL6-RDs and LAMA2-RD, sparing the ambulatory individuals. Results of this study are an indicator of the applicability of the MFM32 both as an outcome measure for clinical trials for COL6-RDs and LAMA2-RD, as well as for tracking changes in motor function in these CMD subtypes over time.