Variants in SHANK3 can accompany Phelan–McDermid syndrome (Berg et al., 2018); PTEN, Cowden syndrome (Goffin et al., 2001); NSD1, Sotos syndrome (Kurotaki et al., 2002); and RAI1, Smith–Magenis syndrome (Slager et al., 2003; Laje et al., 2010). Here, SHANK3 is linked to Cowden disease.