Following this key discovery, a distinct set of PTPN11 mutations was identified in individuals with NS with multiple lentigines (NSML, MIM: PS151100), also known as LEOPARD syndrome (Digilio et al., 2002; Legius et al., 2002), a developmental disorder known to be closely related to NS, providing first evidence of allelic heterogeneity for PTPN11. Here, PTPN11 is linked to Noonan syndrome with multiple lentigines.