Overall, deregulation of the FAT1 gene is associated with FSHD, either as a consequence of DUX4 overexpression, and/or epigenetically encoded in FSHD1 and FSHD2, or through the deletion of a putative enhancer that segregates with contraction-independent FSHD patients. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.