Importantly, FSHD2 patients frequently exhibit mutations in the structural maintenance of chromosomes flexible hinge domain-containing 1 (SMCHD1) gene and sometimes mutations in DNMT3B (mutations not correlated with ICF syndrome; see the related paragraph above) which are most probably responsible for the methylation loss at D4Z4 repeats [85, 86]. This evidence concerns the gene SMCHD1 and ICF syndrome.