Current models of FSHD pathogenesis suggest that D4Z4 contraction (FSHD-1) or other not yet known genetic defects (FSHD-2), results in chromatin modification that could generate aberrant expression of a putative gene encoded by the D4Z4 repeat, termed double-homeobox 4 (DUX4) [8], [12]–[14], or of genes in cis to the D4Z4 array [15], or elsewhere in the genome (in trans). Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.