SMCHD1 and Facioscapulohumeral dystrophy: In this scenario, the identification of SMCHD1, DNMT3B and LRIF1 as causative or modifier genes in FSHD1 and FSHD2 laid the foundations for considering FSHD as a complex disease, in which multiple genes are likely to contribute to the disease heterogeneity and variability (Caputo et al., 2022a) To this regard, NGS approaches are the ideal tool to allow the simultaneous investigation of known FSHD causing (SMCHD1, DNMT3B and LRIF1) and other potential candidate gene modifiers.