Remarkably, although mutations in SOS1 have previously been considered to be more benign in terms of risk of malignancy than those in other genes in the RAS/MAPK pathway (e.g., PTPN11, HRAS, KRAS, and NF1) [Swanson et al., 2008], a significant high occurrence of solid tumors, particularly embryonal rhabdomyosarcoma, has recently been reported in subjects with NS due to a mutated SOS1 allele [Denayer et al., 2010; Hastings et al., 2010; Jongmans et al., 2010]. Here, HRAS is linked to embryonal rhabdomyosarcoma.