Foetal alcohol spectrum disorders (FASD) encompass a wide range of birth defects that are associated with prenatal exposure to alcohol from mild craniofacial defects to foetal alcohol syndrome. The variability of FASD is partly attributed to the timing and level of foetal alcohol exposure but genetic factors may also influence FASD. To identify potential ethanol-sensitive genes, Johann Eberhart and co-workers have been examining the effects of ethanol on known zebrafish craniofacial mutants. On p. 3254, the researchers report that platelet-derived growth factor receptor alpha (pdgfra) heterozygotes and mutants show enhanced craniofacial defects after ethanol exposure. Other results indicate that Pdgfra has a protective effect that is mediated by the mechanistic target of rapamycin (mTor), part of the phosphoinositide 3 kinase (PI3K) signalling cascade. Finally, analysis of a small database recording human craniofacial features and prenatal ethanol exposure links PDGFRA and PDGFRB variants to particular craniofacial phenotypes. Together, these results suggest that combined genetic and environmental inhibition of PI3K/mTOR signalling leads to variability within FASD.