Noonan syndrome is a congenital disorder characterised by a range of clinical problems, including heart defects. It is associated with mutations in components of the RAS-MAPK signalling pathway, most recently N-RAS. Runtuwene et al. now report a newly identified activating N-RAS mutation (I24N) in a patient with features of Noonan syndrome, and explore the effect of this and other activating N-RAS mutations on embryonic development in zebrafish. Their results validate the use of zebrafish for studying mutations associated with Noonan syndrome, and provide support that the developmental defects are caused exclusively by hyperactivation of the RAS-MAPK pathway.