DUX4 and facioscapulohumeral muscular dystrophy: 3 Clinical manifestation of FSHD is highly heterogeneous regarding age of onset, penetrance, muscle group affected, progression and severity which ranges from non-ambulatory to asymptomatic carriers.4 While as of this writing, there are no specific and effective therapies approved for FSHD, the field is burgeoning with DUX4-targeted approaches aiming to reduce DUX4 RNA or protein levels, or to inhibit the DUX4 protein function, with clinical trials already completed, ongoing or expected to begin enrolling soon.