Five homozygotes from 3 families (1 family segregating a deletion of the promoter and 5′-untranslated region of DHRS3, the other 2 a missense variant p.(Val171Met)), manifested a congruent phenotype, including coronal craniosynostosis, dysmorphic facial features, congenital heart disease (4/5 individuals), and scoliosis (5/5 individuals). Here, DHRS3 is linked to craniosynostosis.