FSHD is caused by decreased epigeneticrepression of the D4Z4 macrosatellite array in the subtelomeric region of chromosome 4q,due to either D4Z4 repeat contractions (Lemmers etal., 2010) or mutations affecting trans-acting epigeneticregulators of the D4Z4 repeat such as SMCHD1 (Lemmerset al., 2012), which results in the misexpression of DUX4 mRNA in skeletalmuscle and possibly other somatic tissues. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.