Heritability of MRI lesion volume in CADASIL: evidence for genetic modifiers

Objective: The severity of the phenotype varies markedly among individuals with CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy), a small vessel disease caused by mutations in NOTCH3. However, little is known about the factors underlying this variability. We sought to quantify the contribution of modifying genetic effects to individual differences in the volume of cerebral ischemic lesions. Methods: 151 affected individuals (mean age±SD=45.7±10.4) from 95 unrelated families with CADASIL underwent MRI. Volume of lesions on T2-weighted images and intracranial vol…