Both trisomy 21 and mutations in the Sonic hedgehog (SHH) signaling pathway predispose affected individuals to cerebellar hypoplasia, holoprosencephaly, microcephaly, autism spectrum disorder, cataracts, cleft palate, Hirschsprung disease, hypotonia, atrial and ventricular septal defects, syndactyly, and polydactyly (Andreu-Cervera et al., 2021; Kallen et al., 1996; Kelley and Hennekam, 2000; Moss et al., 2013; Torfs and Christianson, 1998). The gene discussed is SHH; the disease is Hirschsprung disease.