COL4A1/COL4A2 mutations are established monogenic causes of stroke and can present for the first time in adult life with features of cerebral small-vessel disease, including subcortical hemorrhage and ischemic stroke, with lacunar infarcts, leukoaraiosis, and cerebral microbleeds on MRI,6 suggesting a dynamic evolution of COL4A1/2 leukoencephalopathy. This evidence concerns the gene COL4A2 and cerebral small vessel disease.