Upstream RASopathy variants in the NF1, SHP2 (encoded by Ptpn11) and RAS proteins have been shown to modulate PI3K/Akt, PKC and/or Rho/ROCK activity, in addition to the ERK1/2 pathway (Anastasaki and Gutmann, 2014; Brown et al., 2012; Castellano and Downward, 2011; Kaul et al., 2015). This evidence concerns the gene PTPN11 and RASopathy.