Ependymal abnormalities in cerebro-hepato-renal disease of Zellweger

The ependyma in six infants dying with cerebro-hepato-renal (CHR) disease showed similar but less extensive morphological and immunohistochemical abnormalities to those previously demonstrated in lissencephaly/pachygyria. More than two-thirds of the ependyma lining all ventricles was a pseudostratified columnar epithelium resembling midfetal life. Discontinuities did not correlate with minimal ventriculomegaly. Subventricular rosettes were common and not confined to regions of gaps in the overlying ependyma. Subependymal gliosis and glial nodules were absent. Immunoreactivity of ependymal cells for vimentin and GFAP was normal for age, but abnormally positive for S-100 protein and cytokeratin, as in lissencephaly; unlike lissencephaly, the rosettes in CHR disease also are reactive. Ependymal abnormalities may contribute to the pathogenesis of cerebral dysgenesis in CHR disease as in other genetic disorders of neuroblast migration.