One potential explanation is that DUX4 may be a stress and/or hormone responsive gene and FSHD pathology is induced by currently unknown signals that cause short-term bursts of DUX4 expression in increasing cell numbers, leading to the rapid accumulation of muscle pathology (Lim et al., 2020; Rickard et al., 2015). Here, DUX4 is linked to facioscapulohumeral muscular dystrophy.