The two predominantly opposite methylation signatures in ADNP syndrome (the ADNP-1 episignature is largely hypomethylated; the ADNP-2 episignature is hypermethylated) lead us to suspect that each mutation sub-group has unique cellular consequences. The gene discussed is ADNP2; the disease is ADNP-related multiple congenital anomalies - intellectual disability - autism spectrum disorder.