Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy (CADASIL)

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL; MIM 125310) is an inherited cerebrovascular disease whose key features are recurrent transient subcortical ischemic attacks, strokes, migraine with aura, vascular dementia, and diffuse white matter abnormalities detectable through neuroimaging. NOTCH3 gene mutations are causative of the disease and most of them result in a gain or loss of cysteine residue in one of the 34 epidermal growth factor-like repeats in the extracellular domain of the Notch3 protein, thus sparing the number of cysteine residues. To date, more than 130 different mutations in the NOTCH3 gene have been reported in CADASIL patients, of which 95% are missense point mutations. Many polymorphisms have also been identified in the NOTCH3 coding sequence, some of them leading to amino acid substitutions. The aim of the present chapter is to give a detailed description of this pathology.