POG09 CADASIL in a mother and son due to a novel mutation of the NOTCH-3 gene

A 38-year-old man presented with sudden onset atypical chest pain, left-sided pins and needles and slurred speech. Brain imaging demonstrated a left frontal periventricular lesion in keeping with an infarct. His mother had a history of younger onset stroke, with sudden onset vascular cognitive impairment aged 56, followed by progressive strokes and disability. In view of atypical MRI appearances CADASIL was considered and full screening of the NOTCH-3 gene was performed, identifying a mutation in exon 8 p.(Arg427Cys);c.(1279C>T). Subsequent screening identified the same mutation in his mother. This mutation has been previously unreported. Both mother and son presented with profound myalgia and muscle fatigue, 5–10 years prior to the onset of their neurological symptoms. Mitochondrial dysfunction has been reported in CADASIL patients, however in our patient there was no clear evidence of mitochondrial dysfunction on muscle biopsy, typical changes of CADASIL were seen in the small vessels within skeletal muscle.