Holoprosencephaly (HPE; MIM# 236100) is the most frequent congenital brain malformation (1 in 10,000 live births, 1 in 250 conceptuses). It results from incomplete midline division of the prosencephalon between 18th and 28th day of gestation, affecting both the forebrain and the face. The clinical spectrum is very wide, ranging from severe HPE with a single cerebral ventricle and cyclopia to clinically unaffected carriers in familial HPE. Three classic anatomical classes have been described, in decreasing order of severity: alobar, semi-lobar, and lobar HPE. The full spectrum of HPE includes also middle interhemispheric variants (MIH) or syntelencephaly, septopreoptic HPE and microforms characterized by midline defects (e.g., single maxillary median incisor (SMMI) or hypotelorism) without the brain malformations typical of HPE.
SHH