Indications for the importance of DNA methylation in the context of NDDs in humans come from patients suffering from the immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome, a rare autosomal recessive disorder known to be caused by biallelic missense mutations in DNMT3B, leading also to cognitive and intellectual disability (Figure 1 and Table 2; Miniou et al., 1997; Kondo et al., 2000; Jin et al., 2008). The gene discussed is DNMT3B; the disease is ICF syndrome.