Dement Neurocogn Disord.  2016 Mar;15(1):15-19. 10.12779/dnd.2016.15.1.15.

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

• Lee JS
• Ko K
• Oh JH
• Park JH
• Lee HK

• KMID: 2442866
• DOI: http://doi.org/10.12779/dnd.2016.15.1.15

Abstract

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.

Keyword

cerebral autosomal-dominant arteriopathy with subcortical infarcts and leukoencephalopathy; genotype; phenotype; NOTCH3; R544C mutation

MeSH Terms

CADASIL
Cerebral Hemorrhage
Cerebral Infarction
Cerebral Small Vessel Diseases
Dementia
Diagnosis
Genetic Association Studies
Genotype
Headache
Headache Disorders
Humans
Ischemic Attack, Transient
Leukoencephalopathies*
Male
Phenotype
Seizures

Figure

• 

  Fig. 1 Axial MR images in the subjects with R544C mutation. A and D: 3D-T1 weighted image showing multiple lacunes in the basal ganglia and corona radiate. B and E: Fluid-attenuated inversion recovery image showing confluent hyperintensity of external capsule. C and F: Susceptibility Weighted Image showing multiple cerebral microbleeds in the thalamus and corona radiate. Arrow indicates lacunes. Arrow-head points to cerebral microbleeds.

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