In summary, we provide evidence that homozygosity for the 5‘UTR (family 1) and p.(Val171Met) (families 3 and 4) variants in DHRS3 together define a novel RA embryopathy of humans, associated with a reproducible phenotype comprising craniosynostosis, cardiac malformations, and scoliosis among the more distinctive features. This evidence concerns the gene DHRS3 and craniosynostosis.