Abstract

Craniofacial skeletal development in eight human holoprosencephalic fetuses from second trimester abortions were examined by radiography and histology. The whole spectrum of associated facial malformations from anophthalmia through cyclopia, ethmocephaly, cebocephaly, and median cleft lip to short philtrum was represented. Cases with the most severe facial malformations also had the most severely affected facial skeleton. In the facial skeleton, the premaxilla was most often affected; it was absent in seven cases and malformed in the one with only a short philtrum. This and other facial skeletal malformations can be explained as abnormal fusion of the facial bones because of defective development of the nasal cartilage. The occipital bones were normal, but the basicranial skeleton anterior to the spheno-occipital junction was affected in all cases. The findings support the hypothesis that the facial malformations in holoprosencephaly result from disturbance in embryonal life of the mesoderm at the rostral end of the notochord.