Phenotypic Features of Cerebral Autosomal-Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy Subjects with R544C Mutation

BACKGROUND AND PURPOSE: Cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most-common single gene disorder of cerebral small vessel disease. There is no definite evidence of genotype-phenotype correlation in CADASIL. However, recent studies have shown the unique phenotypic feature of NOTCH3 R544C mutation. METHODS: We investigated the phenotypic spectrum of NOTCH3 R544C mutation in 73 CADASIL patients in Jeju between April 2012 and January 2014. RESULTS: Of the 73 subjects from 60 unrelated families included in this study, 40 (55%) were men. The mean age of the subjects was 62.2±12.2 (range 34–86 years). Cerebral infarction was the most frequent manifestation (37%), followed by cognitive impairment (32%), headache (17%), psychiatric symptom (16%), intracerebral hemorrhage (12%), transient ischemic attack (7%), and seizure (1%). The mean age of the subjects with ischemic or hemorrhagic episodes was 64.9±10.9 (range 41–86 years). A diagnosis of dementia was made in 12 subjects (16%). The mean age of the subjects with dementia was 75.6±6.5 (range 62–86 years). About 3% of subjects were unable to walk without assistance at assessment. Only one subject had developed chronic headache before the 40s. CONCLUSIONS: Our data support the hypothesis that CADASIL patients with R544C mutation in Jeju have relatively late onset disease.