We found that the majority of shape variation in Twsg1+/− mouse embryos with intrauterine exposure to a low dose of ATRA was associated with narrowing of the midface as seen in the human microforms (Roessler et al., 1996), Noggin-null mice (Lana-Elola et al., 2011) and in a chick model of HPE (Marcucio et al., 2005; Young et al., 2010). This evidence concerns the gene NOG and holoprosencephaly.