Abstract

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a familial cerebral small vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. Characteristic features include migraine with aura, recurrent subcortical ischaemic events, cognitive impairment and mood disturbances. The disorder is often overlooked or misdiagnosed, and true population prevalence and disease burden is still undetermined. We identified NOTCH 3 mutation positive CADASIL patients from the Northern Ireland genetics databases. We assessed neuroimaging where available and reviewed medical records.

21 gene positive patients were identified within this population. Two mutations accounted for 7/9 pedigrees (arg 182 cys and arg141cys). Mean age of diagnosis was 46 years (range 28–65 years). 10/21 patients had a known family history of CADASIL at time of genetic testing. 19/21 patients were symptomatic: migraine with aura (61%); stroke (52%); TIA (43%); dementia (29%); mood disturbance (29%); seizures (14%). MRI features were highly variable but showed striking similarities within families; some exhibiting changes considered classical of CADASIL and others demonstrating only non-specific white matter changes. One patient exhibited vasculitic type changes on MR angiogram. This study demonstrates the wide variability in the phenotype and MRI features of CADASIL.