SHH and Duane retraction syndrome: Elevated Shh signaling results in various well characterized craniofacial anomalies including anencephaly, hyperterolism, and cleft lip and palate [10,44,45] as well as a disease spectrum in humans called congenital cranial dysinnervation disorders, represented by Duane retraction syndrome (DRS) or Moebius syndrome (MBS) [46,47].