Notably, the increased susceptibility to D4Z4 hypomethylation, associated with a shorter D4Z4 array in FSHD1 and/or SMCHD1 mutations in FSHD2, significantly impacts the disease severity, underscoring the intricate interplay between genetic and epigenetic imbalances in FSHD development [10,11]. The gene discussed is SMCHD1; the disease is facioscapulohumeral muscular dystrophy.