Since the majority of 4A subtelomeres are disease permissive in all forms of FSHD [15, 18], and distinct 4q and 10q D4Z4 hypomethylation profiles are characteristic for FSHD1 and FSHD2, we have developed an assay using a set of three PCR-based bisulfite sequencing (BSS) reactions that together identify the epigenetic signatures for FSHD1, FSHD2, and unaffected subjects. Here, SMCHD1 is linked to facioscapulohumeral muscular dystrophy.