Notochordal remnants in human iniencephaly suggest disturbed dorsoventral axis signaling.

Iniencephaly is a central nervous system malformation in which brain and spinal cord are not normally separated at the level of the foramen magnum. The occipital region is fastened to the back of the body at different levels. The purpose of this study of a 16-week human fetus with iniencephaly and holoprosencephaly was to examine the body axis for notochordal remnants in order to determine if an abnormality of dorsoventral axis signaling may be responsible for the development of the iniencephaly abnormality. This aspect of iniencephaly has not been described previously. Radiographic and histochemical investigations were performed. The fetus described here appeared to exhibit an abnormal notochordal course in the upper lumbar, thoracic, and cervical regions. This finding leads us to the hypothesis that iniencephaly might arise because of deviant gene expression in the embryonic period affecting the dorsoventral orientation of the body axis, anatomically indicated by the notochordal malpositions.