NOTCH3 and Leukoencephalopathy: Nevertheless, some historically high-risk genes for neurodegenerative disorders, such as variants in NOTCH3 that cause CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy), are now considered a spectrum of high and moderate risk conferring variants, and they are counseled accordingly.