The D4Z4 macrosatellite repeat on the permissive 4qA haplotype of chromosome 4q35 is contracted to 1–10 repeat units in FSHD1 patients, accounting for 95% of FSHD, leading to epigenetic derepression of DUX4, which is normally silenced in adult somatic cells. Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.