Berry aneurysms, cirrhosis, pulmonary emphysema, and bilateral symmetrical cerebral calcifications: a new syndrome.

Familial idiopathic nonarteriosclerotic cerebral calcification (FINCC) constitutes a rare but pathologically well defined disorder. Thus far, central nervous system symptoms and signs have been the only recorded expression of this disease. Autosomal dominant and autosomal recessive inheritance have both been postulated as cause. We describe three sibs who had symmetrical cerebral calcifications, but three also had cirrhosis and pulmonary emphysema; two had congenital cerebral aneurysms. All were male and of short stature; they also had delayed development and seizures, and two had other neurologic deficits. One sib died at age 3 years of hepatic failure and portal hypertension. Ruptured cerebral aneurysms led to the death of the other two boys at ages 8 and 13 years. The cerebral calcifications symmetrically involved the basal ganglia and thalami, the dentate nucleus, and the cortical and subcortical areas of the cerebrum. The liver was studied by sequential biopsies in two of the children and in all three by autopsy. Fatty degeneration and portal fibrosis preceded a periportal and micronodular cirrhosis. Severe bilateral pulmonary emphysema was present in one sib at age 12 years, whereas all three had bullae and cysts at autopsy. Ruptured left middle cerebral artery aneurysms were demonstrated in two sibs, and one also had aneurysms of the anterior and posterior communicating arteries. We conclude that in this family FINCC is a complex pleiotropic mendelian mutation, either of autosomal or X-linked recessive nature, whose basic pathogenesis remains unknown but may involve a metabolic defect. This form of FINCC may be a previously undescribed syndrome or a form of FINCC in which extraneural manifestations were previously overlooked.