Although mutations in SHH have been traditionally associated with forebrain patterning malformations such as holoprosencephaly (a disorder in which the embryonic forebrain fails to form two distinct hemispheres), they have also been associated with microcephaly, polymicrogyria (characterized aberrant number of small folds), and schizencephaly (characterized by abnormal slits or clefts), as part of the phenotypic spectrum associated with dysfunctional Shh signaling 113–115. The gene discussed is SHH; the disease is microcephaly.