RAF1 and Noonan syndrome: Another intracellular growth plate-related pathway is the Ras–MAPK signalling pathway, comprising different genes such as PTPN11, SOS1, RAF1, KRAS, BRAF and NRAS. Mutations of this pathway result in a group of syndromes called ‘rasopathies’, including Noonan syndrome.73 These syndromes are characterized by a variable degree of growth impairment that can be associated with other phenotypic features such as facial dysmorphism and a large spectrum of congenital heart defects in cases of Noonan syndrome.74