[CADASIL].

Area of Science:

• Neurology
• Genetics
• Vascular Biology

Background:

• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a rare, inherited cerebrovascular disease.
• Previously reported primarily in Europe and the US, CADASIL is increasingly recognized in Japan.
• Diagnosis relies on clinical presentation, neuroimaging, and genetic testing for Notch3 mutations.

Purpose of the Study:

• To characterize the clinical and genetic features of CADASIL patients in Japan.
• To provide insights into the prevalence and presentation of CADASIL in a Japanese cohort.
• To contribute to understanding the genetic basis and pathogenesis of CADASIL.

Main Methods:

• Review of clinical data from 38 CADASIL families reported in Japan between 1997 and 2008.
• Analysis of patient demographics, neurological symptoms, stroke history, and cognitive impairment.
• Genetic analysis focusing on Notch3 mutations, particularly in exon 4.

Main Results:

• Mean age of onset was 42.3 years, with a wide range (15-71 years).
• Common symptoms included recurrent ischemic attacks (82.2%), migraine (40%), and intellectual impairment (48.9%).
• Notch3 mutations, primarily in exon 4 (71% of families), were identified as the genetic cause.

Conclusions:

• CADASIL is an emerging concern in Japan, with a distinct clinical profile.
• Notch3 mutations are confirmed as the underlying genetic defect in Japanese CADASIL patients.
• Further research is needed to elucidate the pathogenic mechanisms involving Notch3 and granular osmiophilic material (GOM).