For example, mutations that increase MAPK/ERK signaling (e.g. FGFR1-3 (Twigg and Wilkie, 2015; Flaherty et al., 2016), ERF [Twigg et al., 2013]) cause rare syndromic coronal or multisuture craniosynostosis, while mutations that perturb SMAD signaling (e.g. TGFBR1/2 [Loeys et al., 2005], SKI [Doyle et al., 2012], RUNX2 [Mefford et al., 2010; Javed et al., 2008]) cause rare syndromes involving the midline (sagittal and metopic) sutures. Here, RUNX2 is linked to craniosynostosis.