For purposes of identifying craniofacial syndromes which predict brain malformations the face can be regarded as developing from 2 sources. The median and paramedian structures derive from the embryonic segment of the face, termed the frontonasal prominence. The lateral structures of the face derive from the branchial arches. Certain patterns of median plane facial anomalies predict a severe brain malformation, while other patterns, although producing equally grotesque facial malformations, bear little association with a malformed brain. Orbital hypotelorism may occur in a variety of syndromes with microcephaly. When combined in typical patterns with other median plane facial defects, the patient almost certainly has holoprosencephaly, and has a poor prognosis for useful psychomotor development and survival. To the current knowledge of the author, every patient with orbital hypotelorism and total aplasia of the intermaxillary segment has a severely malformed brain. These patients, with only a rare exception, make no useful psychomotor progress and die in infancy. Orbital hypertelorism implies an increased risk of a neurologically abnormal patient, but neither the mental deficiency nor the prognosis for survival are as poor as in hypotelorism. When hypertelorism is combined with certain median plane facial anomalies the patient has the median cleft face syndrome and most likely has normal mentality, or only mild retardation, and has a normal prognosis for survival.