A case of CADASIL without characteristic anterior temporal pole lesion diagnosed by skin biopsy

Abstract

A 40 year-old man with migraine presented cerebral ischemic attacks several times in one year. He had no risk factors for cerebrovascular disease including hypertension, but had strong family history suggesting autosomal dominant inheritance. A brain MRI on T 2 weighted and FLAIR images revealed patchy and confluent hyper intensity areas in the subcortical white matters and bilateral external capsules, while no anterior temporal pole lesions characteristic of CADASIL (cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy) were detected. His skin biopsy demonstrated granular osmiophilic materials (GOM) on the basement membrane of the vascular smooth muscle cells in dermis as shown by an electron microscope. The following mutational analysis of the Notch3 gene disclosed a missense mutation of p.Arg133Cys in exon 3. Molecular diagnosis of CADASIL may be time consuming because Notch3 is a huge gene and mutations may occur at multiple sites. GOM on skin biopsy is diagnostic especially in cases where anterior temporal pole involvement on MRI is negative.