SMAD6 and craniosynostosis: Moreover, because non-syndromic sagittal and metopic craniosynostosis comprise half of all craniosynostoses (Slater et al., 2008; Greenwood et al., 2014), SMAD6/BMP2 genotypes are inferred to account for ~3.5% of all craniosynostosis, and are likely rivaled in frequency only by mutations in FGFR2 as the most frequent cause of all craniosynostoses (Twigg and Wilkie, 2015).