Clinical and Genetic Aspects of CADASIL

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), a hereditary cerebral small vessel disease caused by mutations in NOTCH3, is characterized by recurrent stroke without vascular risk factors, mood disturbances, and dementia. MRI imaging shows cerebral white matter (WM) hyperintensity, particularly in the external capsule and temporal pole. Missense mutations related to a cysteine residue in the 34 EGFr on the NOTCH3 extracellular domain (N3ECD) are a typical mutation of CADASIL. On the other hand, atypical mutations including cysteine sparing mutation, null mutation, homozygous mutation, and other associate genes are also reported. From the viewpoint of gain of function apart from Notch signaling or loss of function of Notch signaling, we review the research article about CADASIL and summarized the pathogenesis of small vessel, stroke, and dementia in this disease.