SMCHD1 and Facioscapulohumeral dystrophy: However, this is fundamentally different from the FSHD-intrinsic clinical variability caused by molecular heterogeneity from the FSHD1 locus itself, as exemplified by our previous findings of mutations in the SMCHD1 gene acting as a genetic modifier of severity for FSHD1 patients [46] and of patients carrying a 18p deletion encompassing SMCHD1 gene that in presence of a contracted 4qA D4Z4 allele display features of FSHD in association with uncommon features [47].