Diagnosing CADASIL using MRI: evidence from families with known mutations of Notch 3 gene

Clinical data and MRI findings are presented on 18 subjects from two famili es with neuropathologically confirmed CADA-SIL. DNA analysis revealed mutat ions in exon 4 of Notch 3 gene in both families. All family members with mu tations in Notch 3 gene had extensive abnormalities on MRI, principally les ions 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; n one 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 re viewed. However, a wide differential diagnosis exists for the MRI appearanc es of CADASIL, including multiple sclerosis and small-vessel disease second ary to hypertension. The definitive diagnosis cannot be made on MRI alone a nd requires additional evidence, where available, from a positive family hi story and by screening DNA for mutations of Notch 3 gene.