NOTCH3 and snowflake vitreoretinal degeneration: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most frequent monogenic form of SVD and is caused by mutations in the NOTCH3 gene 135, leading to NOTCH3 protein accumulation, white matter lesions (WML), and subcortical infarcts.