Neuropathology of holoprosencephaly

Abstract

Holoprosencephaly (HPE) is a brain malformation which results from a primary defect in induction and patterning of the rostral neural tube during early embryogenesis and usually considered as an impaired cleavage of the prosencephalon. The review of neuropathologic findings highlights a complex malformation involving not only the prosencephalon but also the whole brain, the eyes, and the cerebral vascularization. The classical form of HPE is divided in three sub-types according to DeMyer classification, although the spectrum is far wider, ranging from the most severe, aprosencephaly/atelencephaly, to milder forms such as syntelencephaly and to the less severe ends of the spectrum. Macroscopy and microscopy abnormality patterns are described extensively, allowing a comparison of the anatomic features between each form. Disturbances observed in the main cerebral structures including the basal ganglia, the commissures, the hippocampus, the brainstem, the cerebellum, and spinal cord are reviewed. Macroscopic and microscopic features of the ophthalmic anomalies are described, as well as brain vascular and associated central nervous system malformations.