Snake under the skull sign is a vascular anomaly seen in holoprosencephaly.
Due to the defect in the cleavage of the two hemispheres there is a fusion of the frontal lobes. This band of abnormal cortical tissue causes forward displacement of the anterior cerebral artery, so that it lies in the inner side of the frontal bones.
On a mid sagittal view, the anterior cerebral artery is seen to be displaced further anteriorly to lie underneath the frontal bone giving an appearance of a serpent under the calvarium.
Semilobar and alobar holoprosencephaly are easily differentiated; however differentiation between lobar holoprosencephaly and septooptic dysplasia is difficult. This sign will help in differentiating between the two.