The relation of leukoencephalopathy, lacunar infarcts, micro- and macro-bleeds to a defect in collagen IV Al gene was examined in a family with the mutation and autosomal dominant porencephaly followed at VU University Medical Center, Amsterdam, the Netherlands. Porencephaly was diagnosed in the mother at age 24 years, while her 2 children had symptoms and signs of porencephaly in infancy. The mother developed recurrent strokes beginning at age 42 years. All 3 patients had leukoencephalopathy. MRI showed lacunar infarcts, and micro- and macro-bleeds. Electron microscopy of skin vessels showed interruptions and thickening of the basement membrane. A heterogeneous mutation in the collagen IV Al gene, a component of the vascular basement membrane, was found in all 3 patients, but was absent in the father and in 192 matched Dutch controls. This mutation is a risk factor for a microangiopathy, resulting in perinatal hemorrhage and porencephaly, leukoencephalopathy, and later onset ischemic and hemorrhagic strokes. [1]

COMMENT. Porencephaly, a term first coined by Heschl in 1859 to designate a congenital defect extending from the surface of the brain to the lateral ventricle, was later defined as any cavity within the brain tissue, with or without extension to the ventricle or subarachnoid space, of prenatal or postnatal origin (Norman RM. In Greenfield’s Neuropathology. Baltimore, Williams & Wilkins, 1963). Yakovlev and Wadsworth (1946) described schizencephalic porencephalies of developmental origin and encephaloclastic porencephalies caused by destruction of cerebral tissue. A wide variety of etiological factors and clinical findings are reported [2]. Hemorrhagic infarction following a germinal matrix hemorrhage in a preterm infant is a frequent destructive cause. Other causes include trauma, vasculopathy secondary to maternal cocaine abuse or congenital infections such as cytomegalic inclusion disease, bleeding disorders, including factor V Leiden and collagen IV A1 mutation with microangiopathy, as in familial autosomal dominant porencephaly, described in the above report.