SHH and holoprosencephaly: The significance of SHH in human brain development is illustrated by the dramatic consequences of SHH-pathway gene disruption, which include holoprosencephaly, seizure disorders, language or cognitive impairment, Down syndrome, hyperactivity, and schizophrenia (Heussler et al. 2002; Nanni et al. 1999; Belloni et al. 1996; Odent et al. 1999; Santiago et al. 2006; Currier et al. 2012; Betcheva et al. 2013).