CADASIL, CARASIL, CARASAL

Cerebral small vessel disease (SVD) and its major clinical consequences, stroke and vascular dementia, represent an increasing health problem in aging societies. The role of genetic factors in SVD etiology is well established and a number of Mendelian forms, including CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) and CARASIL (cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy), have been described.1 However, only limited progress has been made in the last decades in identifying the underlying gene defects. The advent of deep DNA sequencing technologies has tremendously facilitated the search for disease-causing variants, a recent example being the identification of heterozygous HTRA1 mutations in several families with a previously unknown dominant form of SVD.2 In a study by Bugiani et al.3 published in this issue of Neurology ®, a whole-exome sequencing approach was used to detect the genetic cause of an adult-onset, dominantly inherited leukoencephalopathy of unknown origin in 2 families.