The specific association of CHD5 defects with craniosynostosis remains puzzling based on the reported preferential expression of this gene in brain and testis, but possibly suggests that CHD5 might be expressed more broadly at some stages of embryonic development or that craniosynostosis is linked to an indirect effect of CHD5 alterations on gene expression programs that coordinate boundary formation or differentiation of overlying cranial neural crest. This evidence concerns the gene CHD5 and craniosynostosis.