Abstract
Hereditary small vessel diseases of the brain with autosomal dominant inheritance can be divided into two types, CADASIL caused by the NOTCH3 mutation (NOTCH-C) and the NOTCH3 non-related CADASIL-like syndrome (Non-NOTCH-C). Portuguese-French family and Swedish family were reported as a new hereditary small vessel diseases of the brain not related NOTCH3. Clinicoradiological features in Non-NOTCH-C were compared with those in NOTCH-C. Subjects included 21 Japanese patients with multiple lacunar infarctions in 18 families with autosomal dominant inheritance. After screening 1-24 exon (s) of NOTCH3 using denaturing high-performance liquid chromatography, mutations were confirmed by direct sequencing. Of the 21 Japanese patients, 12 were determined to have NOTCH-C and 9 to have Non-NOTCH-C. Although Non-NOTCH-C patients had significantly less granular osmiophilic material in skin biopsies and less white matter lesions at the temporal pole identified by MRI, the clinical course and symptoms in Non-NOTCH-C patients resembled those in NOTCH-C patients. We report the identification of CADASIL-like syndrome not related to the NOTCH3 mutation in Japan as well as Sweden and France.
