SMAD6 mutations were significantly more frequent in kindreds with any metopic craniosynostosis (10 of 78, 12.8%) compared to those with isolated sagittal craniosynostosis (3 of 113, 2.7%; p=8.1 × 10–3 by Fisher’s exact test, odds ratio 5.3). Here, SMAD6 is linked to craniosynostosis.