Further, mutations in human ZIC2 result in holoprosencephaly (HPE), a forebrain defect where the cerebral hemispheres fail to separate during development [50,51] and HPE phenotypes have been connected to aberrant RA signaling, thus providing a plausible link between Zic2 and retinoic acid metabolism [29,36,52,53]. The gene discussed is ZIC2; the disease is holoprosencephaly.