TGIF1 and holoprosencephaly: Isolated HPE presents a high genetic heterogeneity and to date heterozygous mutations in 14 genes have been identified in HPE patients, 4 major genes (Sonic hedgehog or SHH, ZIC2, SIX3, TGIF1) and 10 genes considered as minor genes (PTCH1, TDGF1, FAST1, GLI2, DISP1, FGF8, GAS1, CDON, NODAL and DLL1) [4–7].