A major obstacle facing FSHD clinical trials targeting DUX4 expression is the lack of any independently validated circulating molecules that can reproducibly be used as predictive, prognostic and/or pharmacodynamic biomarkers (Banerji, 2020; Harafuji et al., 2013; Heier et al., 2020; Matsuzaka et al., 2014; Petek et al., 2016; Signoelli et al., 2020; Statland et al., 2014). This evidence concerns the gene DUX4 and facioscapulohumeral muscular dystrophy.