Arguing against a direct genotype-phenotype association is the finding that a diverse group of syndrome-associated gene mutations have been identified in syndromic patients presenting with CGCL-like lesions of the jaws; including PTPN11, SOS1, BRAF, and MEK1 in Noonan Syndrome (13), BRAF and MEK1 in cardiofacio-cutaneous syndrome (13), and PTPN11 in Noonan syndrome with multiple lentigines (14). This evidence concerns the gene MAP2K1 and Noonan syndrome.