シンポジウム03―1 神経難病の克服―単一遺伝子病からのアプローチ― CARASIL―臨床概念の確立―

CARASIL (Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy) is the second known single-gene disorder directly affecting cerebral small vessels. The acronym CARASIL was proposed by Bowler and Hachinski (1994), based on its recessive inheritance and resemblance to CADASIL (R instead of D). The first CARASIL patients were most probably described in preliminary reports in 1965-66, and later in Japanese and English articles in 1969-1976. In 1985, the author and colleagues reported on another family of three brothers with strikingly similar clinical features, including not only neurological symptoms but also recurrent acute lumbago and premature alopecia, and cerebral white matter disease on CT scans, proposing that these characteristics can constitute a new systemic syndrome. According to our clinical and pathological/neuroradiological criteria, similar patients have been reported, almost exclusively from Japan, with a total reaching 50 until today. In five consanguineous families including ours, Hara et al. (2009) identified homozygous mutations in the HTRA1 gene on chromosome 10q25. Since no founder haplotype has been identified, the author and allied researchers suspect that this disorder will be found more widely. This review summarizes the historical background, epidemiology, characteristic clinical findings, neuroimaging, and clinical perspectives after the gene identification of this disorder.