Holoprosencephaly (HPE) is a complex brain malformation resulting from incomplete cleavage of the prosencephalon, occurring between the 18th and 28th day of gestation, and affecting both the forebrain and face, which results in neurological manifestations and facial anomalies of variable severity.
The etiology is very heterogeneous: from chromosomal abnormalities (such as trisomy 13), known syndromes (such as Smith-Lemli-Opitz syndrome, Charge syndrome) to environmental factors (maternal diabetes or hypocholesterolemia during gestation). In non-chromosomal non-syndromic HPE, at least 14 genes have been implicated: 4 major genes (SHH (7q36), ZIC2 (13q32), SIX3 (2p21), TGIF (18p11)) and 10 minor genes (PTCH1 (9q22), GLI2 (2q14), FOXH1 (8q24), TDGF1 (3p21), DISP1 (1q42), NODAL (10q22), FGF8 (10q24), GAS1 (9q21), DLL1 (6q27), and CDON (11q23-q24)) .
