Heterozygous mutations in Sonic Hedgehog (SHH) pathway components are found in both inherited and sporadic HPE, including SHH itself, the primary receptor PTCH1, the co-receptors CDON (also called CDO) and GAS1, and the transcription factor, GLI2 [6], [8]–[11]. This evidence concerns the gene SHH and holoprosencephaly.