Inheritance: autosomal dominant
Gene affected: NOTCH3 on Chromosome 19 (19p13.1) at nucleotide 259 (C259T)
Clinical features:
(1) migraine headaches, often starting in early adulthood
(2) stroke-like episodes in the fifth or sixth decades
(3) aphasia
(4) hemiparesis
(5) vascular dementia
Imaging study findings:
(1) multiple subcortical infarcts
(2) multifocal white matter disease, sometimes symmetrical
Pathologic finding: non-atherosclerotic, non-amyloid small vessel vasculopathy with eosinophilic, granular material replacing smooth muscle. These changes can be seen in skin biopsies involving small dermal blood vessels.
Differential diagnosis:
(1) multiple sclerosis
(2) other small vessel vasculopathies (atherosclerosis, cerebral amyloid arteriopathy, vasculitis)
