A consequence of the epigenetic disruption at 4q35 in FSHD1 and FSHD2 is the increased expression and altered splicing of the double homeobox 4 (DUX4) gene to generate the DUX4-fl (DUX4-full length) mRNA in FSHD skeletal muscle, which results in aberrant expression of DUX4-FL and its downstream target genes with consequent pathology [17,30-36]. This evidence concerns the gene SMCHD1 and facioscapulohumeral muscular dystrophy.