Although the defining medial forebrain deficiency of true HPE has been identified in several individuals with single-allele GLI2 mutations, most cases involve more subtle abnormalities, such as pituitary deficiency and/or facial dysmorphology (Bear et al., 2014; Roessler et al., 2003; Bertolacini et al., 2012; Franca et al., 2010; Rahimov et al., 2006). This evidence concerns the gene GLI2 and holoprosencephaly.