title: Diagnosing CADASIL using MRI: evidence from families with known mutations of Notch 3 gene.
abstract: Clinical data and MRI findings are presented on 18 subjects from two families with neuropathologically confirmed CADASIL. DNA analysis revealed mutations in exon 4 of Notch 3 gene in both families. All family members with mutations in Notch 3 gene had extensive abnormalities on MRI, principally lesions in the white matter of the frontal lobes and in the external capsules. Of several family members in whom a diagnosis of CADASIL was suspected on the basis of minor symptoms, one had MRI changes consistent with CADASIL; none of these cases carried a mutation in the Notch 3 gene. MRI and clinical features that may alert the radiologist to the diagnosis of CADASIL are reviewed. However, a wide differential diagnosis exists for the MRI appearances of CADASIL, including multiple sclerosis and small-vessel disease secondary to hypertension. The definitive diagnosis cannot be made on MRI alone and requires additional evidence, where available, from a positive family history and by screening DNA for mutations of Notch 3 gene.
authors.affiliation: Department of Neuroradiology, Royal London Hospital, Whitechapel, UK.
authors.forename: S J
authors.initials: SJ
authors.lastname: Chawda
authors.forename: R P
authors.initials: RP
authors.lastname: De Lange
authors.forename: M D
authors.initials: MD
authors.lastname: Hourihan
authors.forename: S F
authors.initials: SF
authors.lastname: Halpin
authors.forename: D
authors.initials: D
authors.lastname: St Clair
mesh_terms: D000328:Adult; D000368:Aged; D002540:Cerebral Cortex / Q000473:pathology*; D015161:Dementia, Multi-Infarct / Q000175:diagnosis* / Q000235:genetics*; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D010375:Pedigree