Osteogenesis imperfecta type II: microvascular changes in the CNS

Osteogenesis imperfecta, type II is a rare hereditary disease of connective tissue with abnormalities of type I collagen. It is invariably fatal in the neonatal period. We report 2 cases with abnormal cerebral cortical white matter consisting of abundant, perivenous microcalcifications, proliferated vascular endothelium and focal aggregates of germ cells. Histochemically, microcalcifications lie within nodules composed of a PAS-positive, carbohydrate-rich matrix. This matrix also stains with alcian blue suggestive of a proteoglycan component. Immunoperoxidase staining reveals that some of these nodules are surrounded by type I collagen. Adjacent vessels show endothelial proliferation associated with markedly redundant basement membranes as confirmed by reactivity with anti-type IV collagen. Although the cerebral cortex has a normal neuronal cytoarchitecture, the areas that appear externally dysplastic overlie nests of germ cells within the underlying white matter suggestive of impaired migration. These changes most likely occurred during the third trimester and may involve abnormal interactions of proteoglycans and the extracellular matrix with collagen.