Genetic Causes of Cerebral Small Vessel Diseases

Abstract

Cerebral small vessel disease (CSVD) includes various entities affecting the brain and, often, systemic small arteries, arterioles, venules, and capillaries. The underlying causes of CSVD are different, and some of them are genetic. Monogenic CSVDs are responsible for 1%–5% of all strokes and for several other disturbances. Despite many genes being involved, the phenotypes of monogenic CSVD partly overlap. Given that the genetic testing for different diseases can be challenging and time-consuming, the practicing neurologist should be adequately informed of the genetic background of CSVD and should be able to select patients to undergo genetic assessment and the genes to be analyzed. The purpose of this review was to summarize clinical, neurologic and non-neurologic, and neuroimaging features of monogenic CSVD and to provide a flowchart to be used in clinical practice to guide neurologists in this field. The proposed flowchart and the relative tables can be applied to 3 different settings, depending on the presentation: (1) ischemic stroke and/or transient ischemic attack, (2) cerebral hemorrhage, and (3) other neurologic, non-neurologic, and/or neuroimaging features of monogenic CSVD, in the absence of stroke syndromes because of infarction or hemorrhage.