NOTCH3 and Stroke: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic form of stroke, resulting in early onset lacunar stroke and dementia.1,2 It is caused by characteristic cysteine-altering variants in the epidermal growth factor-like repeat (EGFR) domains of the NOTCH3 gene.3 The clinical phenotype is highly heterogeneous with stroke onset ranging from the fourth to eighth decade.4