Genetic considerations in cerebral small vessel diseases

Abstract

Cerebral small vessel disease (CSVD) encompasses a broad clinical spectrum united by pathology of the small vessels of the brain. CSVD is commonly identified using brain magnetic resonance imaging with well characterized markers including covert infarcts, white matter hyperintensities, enlarged perivascular spaces, and cerebral microbleeds. The pathophysiology of CSVD is complex involving genetic determinants, environmental factors, and their interactions. While the role of vascular risk factors in CSVD is well known and its management is pivotal in mitigating the clinical effects, recent research has identified novel genetic factors involved in CSVD. Delineating genetic determinants can promote the understanding of the disease and suggest effective treatments and preventive measures of CSVD at the individual level. Here we review CSVD focusing on recent advances in the genetics of CSVD. The knowledge gained has advanced understanding of the pathophysiology of CSVD, offered promising early results that may improve subtype identification of small vessel strokes, has led to additional identification of mendelian forms of small vessel strokes, and is getting closer to influencing clinical care through pharmacogenetic studies.