Although IGF-II has been shown to regulate neuronal growth and differentiation in animal models and cell lines (Sullivan et al., 2008; Bracko et al., 2012), only a small proportion of patients with Russell–Silver syndrome with loss of methylation (LOM) of the 11p15 ICR1 telomeric domain (including IGF2) leading to reduced IGF-II gene expression in tissues, show developmental delay (Netchine et al., 2007). This evidence concerns the gene IGF2 and Global developmental delay.