The direct pathway effector genes PTCH1 (Ming et al. 2002; Ribeiro et al. 2006), CDON (Bae et al. 2011), DISP (Roessler et al. 2009), GAS1 (Ribeiro et al. 2010; Pineda-Alvarez et al. 2012), and GLI2 (Roessler et al. 2003), as well as other genes also cause various forms of HPE either alone or in compound heterozygous combination (Dubourg et al. 2016; Mouden et al. 2016). The gene discussed is PTCH1; the disease is holoprosencephaly.