Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL). Clinical, neuroimaging, pathological and genetic study of a large Italian family.

Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy (CADASIL) is a rare hereditary stroke disease. The gene has been recently mapped, in two French families, on chromosome 19q12 between two highly polymorphic genetic markers. We report on a new large Italian family affected with this disease, which is characterized by recurrent stroke episodes, focal neurological deficits progressing to pseudo-bulbar palsy, and dementia. Multiple deep infarcts and diffuse leucoencephalopathy were revealed by MRI and brain histopathology showed abnormalities of arterial media. A genetic study performed with microsatellite markers from region 19q12 showed that the disease locus lies in an interval largely overlapping that already described and is closely linked to two microsatellite markers, D19S212 and D19S222. A joint analysis of genotypic and phenotypic data shows that diffuse leucoencephalopathy is a reliable sign of the disease in otherwise normal 50%-risk subjects over the age 30 years and that penetrance of stroke episodes or dementia is most likely complete around age 60 years.