PTPN11 and Noonan syndrome with multiple lentigines: LEOPARD syndrome, which is also inherited in an autosomal dominant fashion and is distinguished from Noonan syndrome by the presence of multiple lentigines (café-au-lait spots), results only from a small set of PTPN11 missense mutations, which are believed to be associated with the loss, rather than with the gain, of SHP2 function (Digilio et al., 2002).