Interestingly, while gain-of-function mutations in SHP2 dominate the spectrum in Noonan syndrome patients, dominant-negative, loss-of-function mutations abrogating phosphatase activity occur in LEOPARD syndrome patients and rather seem to divert RTK derived signals into the PI3K axis and highlight the adaptor functions of this phosphatase [65]. Here, PTPN11 is linked to Noonan syndrome with multiple lentigines.