Structural malformations of the brain are an important cause of childhood 
mortality and morbidity, with the latter having long-term financial and 
psychosocial implications for the affected child and family. Holoprosencephaly 
(HPE) is a severe brain malformation characterized by abnormal cleavage of the 
prosencephalon in the 5th gestational week. Aprosencephaly and atelencephaly 
occur earlier because of failure in the formation of the prosencephalon and 
telencephalon, respectively. The HPE holoprosencephaly spectrum classically 
includes alobar, semilobar, and lobar forms, although there are no clear-cut 
defining features. The middle interhemispheric variant (MIH), also known as 
syntelencephaly, is classified as a variant of HPE holoprosencephaly with 
midline interhemispheric fusion. Other conditions sometimes included in the 
spectrum of HPE holoprosencephaly include septo-optic dysplasia (SOD); "minimal" 
HPE holoprosencephaly , which is associated with subtle craniofacial 
malformations and mild developmental delay; and microform HPE holoprosencephaly 
, which by definition excludes brain involvement. The focus of this article will 
be on the spectrum of findings visible in fetal manifestation of the HPE 
holoprosencephaly spectrum. Brain embryology; the imaging characteristics, 
epidemiology, and embryology of HPE; and the more common associated anomalies, 
particularly those of the face ("the face predicts the brain") are reviewed. 
Recognition of these anomalies is important for accurate parental counseling, 
since the prognosis is poor but not invariably lethal; children with the milder 
forms may live well into their teens with severe developmental delays, endocrine 
dysfunction, and disrupted homeostasis. Available data on outcome in surviving 
children are summarized. Illustrative fetal ultrasonographic and magnetic 
resonance images are presented with clinical, autopsy, and postnatal imaging 
correlation.