In summary, we found that healthy myotubes exhibit specific adaptive responses to EPS, which is impaired in FSHD patient and mutant myotubes as well as myotubes overexpressing the DUX4 target, LEUTX, indicating the cell autonomous defect of FSHD associated with DUX4 target gene activation. This evidence concerns the gene LEUTX and Facioscapulohumeral dystrophy.