Inheritable mutations in components of the SHH signaling pathway have been associated with human HPE, including mutations in SHH, in its receptor patched 1 (PTCH1), or in downstream transcription factors, such as GLI family zinc finger 2 (GLI2), SIX homeobox 3 (SIX3) and zinc-finger protein of the cerebellum 2 (ZIC2) (Roessler and Muenke, 2010). The gene discussed is PTCH1; the disease is holoprosencephaly.