In individuals with FSHD, the epigenetic repression of DUX4 is incomplete as a consequence of having fewer than 11 D4Z4 repeats (FSHD type 1, FSHD1) or mutations in trans-acting chromatin repressors of D4Z4 (FSHD type 2, FSHD2), either of which results in ectopic expression of DUX4 in skeletal muscle when combined with a permissive chromosome 4qA haplotype that provides a polyadenylation site for the DUX4 mRNA (Lemmers et al., 2012; Lemmers et al., 2010; van den Boogaard et al., 2016). Here, SMCHD1 is linked to facioscapulohumeral muscular dystrophy.