Background: Disease progression in childhood-onset FSHD remains poorly elucidated. Improved understanding of how to measure change in function is required to support design of pediatric clinical trials.
Methods: This single-site Australian natural history study evaluated prospective longitudinal outcomes in pediatric FSHD over 2-years. Performance-based functional measures (FSHD-COM Peds, PUL, 6MWD, timed function, muscle strength, reachable workspace) were evaluated on three occasions 12-months apart.
Results: Eighteen children aged (6-19 yrs) with genetically confirmed symptomatic FSHD1 with disease onset less than 18 years, completed the two-year study. The cohort was sub-divided into two groups based upon the size of the repeat contraction in the D4Z4 region: Group A (n=7) included those with a large contraction (1-3 D4Z4 repeats), and Group B (n=11) those with a moderate contraction (4-7 D4Z4 repeats). Baseline demographics included: 58% male sex, 95% had facial and scapula weakness, 74% had a positive Beevor sign, 47% had pelvic weakness, 32% had Sensorineural hearing loss but this was only seen in Group A participants.
Taken as a whole cohort, there was a statistically significant change over 12 and 24 months in the Sit To Stand, Ascend 4 Stairs and PUL outcomes, albeit with a significantly greater rate of deterioration in Group A. There was a clear difference between the two cohorts: those in Group A had a deterioration in the FSHD-COM score, 6MWD, 10mW/R, time to descend 4 stairs, PUL and time to rise from supine to standing over two years compared to improvements in those same outcomes seen in Group B.
Conclusion: Results from the iFSHD-LOS study support the hypothesis that children with FSHD caused by large repeat contractions are more severely impacted by disease progression. Although small numbers, this study also adds to the growing natural history data to support inclusion of paediatric participants in future clinical trials.