Morphological features of holoprosencephaly

Abstract

The gross and microscopic features of holoprosencephaly are described on the basis of five representative cases of the alobar and semilobar types, which were investigated by autopsy and/or magnetic resonance imaging. Alobar holoprosencephaly was distinguished from the semilobar type by its gross morphology: the brain neither separated horizontally into the hemispheres nor differentiated axially into the telencephalon and diencephalon. Dorsal cyst, which communicated with the prosencephalic common ventricle through a horseshoe‐shaped cerebral mantle defect, was present in all cases. The wall of the cyst, called the ‘dorsal sac’, consisted of ependymal remnants and leptomeninges, in which a layer of dysplastic cerebral tissue or heterotopic glioneural tissue was included in some cases. The dorsal sac extended from the hippocampal ridge and attached posteriorly to the epithalamic structure. The cerebral cortex showed abnormally formed convolutions with agyria, pachygyria or polymicrogyria in all the cases examined, without distinction between the alobar and semilobar types. The microscopic features of these cortices were poorly formed lamination, marginal glioneural heterotopia and periventricular aggregates of neuroblasts. Glomerular structures, which Mere devoid of neurons and consisted of fine dendrites and axons, were found in three cases of this series. These abnormal cortical structures, resulting from disordered neuronal migration, were considered characteristic microscopic findings of the holoprosencephalic brain. The current classification system advocated by DeMyer and Zeman, which depends on surface morphology, does not reflect the maturity of the brain as investigated histopathologically in this series.