D4Z4 repeats are normally in a repressed chromatin state in somatic cells prohibiting the expression of DUX4 in muscle cells, but become partially derepressed when the repeat is contracted to a size of 1–10 D4Z4 units (FSHD1: ~ 95% of FSHD individuals) and/or in the presence of damaging variants in specific D4Z4 chromatin repressors in combination with an intermediately-sized D4Z4 repeat (FSHD2: ~ 5% of individuals)2,9–11. The gene discussed is SMCHD1; the disease is Facioscapulohumeral dystrophy.