CADASIL: A monogenic condition causing stroke and subcortical vascular dementia

Mutations in Notch3 are the cause of cerebral autosomal dominant
arteriopathy with subcortical infarcts and leukoencephalopathy
(CADASIL), an inherited small vessel disease leading to subcortical
strokes and vascular dementia. The phenotypic presentation is
variable but remarkable for a high frequency of migraine with aura.
Magnetic resonance images show a microangiopathic pattern of
lesions. Prominent involvement of the temporopolar white matter and
involvement of the temporopolar arcuate fibers are conspicuous
findings seen in many patients, The underlying angiopathy is
characterized by a unique type of ultrastructural basal lamina
deposits and by degeneration of vascular smooth muscle cells which
are the major source of Notch3 expression. In line with these
findings there is evidence for a functional impairment of vascular
smooth muscle cells. CADASIL has opened a new perspective in
studying basic mechanisms of vessel wall degeneration and ischemic
tissue damage related to small vessel disease. Copyright (C) 2002
S. Karger AG, Basel.