Both TGIF and ZIC2 are mutated in holoprosencephaly, a disorder caused by a failure in embryonic forebrain development (Brown et al, 1998; Gripp et al, 2000), whereas MYCN mutations cause Feingold and megalocephaly syndromes, which are associated with reduced and increased brain size, respectively (van Bokhoven et al, 2005; Kato et al, 2019). This evidence concerns the gene ZIC2 and holoprosencephaly.