SHH and holoprosencephaly: The genes known so far to be associated with HPE in humans and producing HPE phenotypes in mice upon genetic manipulation, include SHH, PTCH1, GAS1, DISP1, GLI2, SIX3, NODAL, TGIF, FOXH1 and ZIC2[2], [5] and they fall into three major signalling pathways: the sonic hedgehog (Shh)-, the Nodal- and the bone morphogenetic protein (BMP)-signalling pathway [4].