In our cohort, we found that out of 34 index cases with classical FSHD phenotype carrying normal-sized D4Z4 alleles at 4q (FSHD2), 18 (52.9%) displayed CpG methylation levels higher than the 25% cutoff, assessed with the MRSE2 assay. Here, SMCHD1 is linked to facioscapulohumeral muscular dystrophy.