SMCHD1 and facioscapulohumeral muscular dystrophy: Full-length DUX4 RNA is not always detectable in muscle tissue from FSHD patients, and it is present in some unaffected individuals with normal D4Z4 repeat arrays, suggesting that a second factor or mutation is required for pathogenesis.21–22 The recent discovery of a causative gene (SMCHD1) for FSHD2 (a disease identical to FSHD in terms of phenotype and chromosome 4q hypomethylation, but without contraction of the D4Z4 array) also supports a 2-hit hypothesis and further highlights the importance of both the genetic and epigenetic aspects of this disease.23,24