HTRA1-related cerebral small-vessel disease causes cerebral microbleeds on the brainstem surface

Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) has recently been known as HTRA1-related cerebral small-vessel disease (CSVD), it is caused by variants in HTRA1. Recently, it has been reported to develop in heterozygotes with some variants of the gene. Multiple prospective studies have reported that the frequency of heterozygous HTRA1 variants developing CSVD is 2 - 6.5 % in CARASIL. Heterozygous variant cases lack unique clinical features, have an older age of onset, and are difficult to detect. Characteristic findings are required to identify such cases.