NEW PHENOTYPE OF THE CEREBRAL AUTOSOMAL-DOMINANT ARTERIOPATHY MAPPED TO CHROMOSOME-19 - MIGRAINE AS THE PROMINENT CLINICAL-FEATURE

A survey was carried out on a large family presenting the symptoms of familial arteriopathy (CADASIL) recently mapped to chromosome 19. This is characterised clinically by recurrent subcortical infarcts develop ing into pseudobulbar palsy and subcortical dementia, and radiological ly by early MRI abnormalities. To characterise this familial condition , 43 members older than 20 years and spreading over four generations w ere studied clinically (31 living, 12 deceased), genetically, and radi ologically by MRI (n = 31). Twenty out of 43 were found to be clinical ly symptomatic and of these 13 out of 31 had MRI abnormalities. Geneti c studies mapped this condition to the locus of CADASIL (lod score > 3 ). The natural history suggests a chronological clinicoradiological st aging of this phenotype of CADASIL: stage 1 between 20 and 30 years wi th frequent migraine-like episodes and well delineated lesions of the white matter; stage II between 40 and 60 years with stroke-like episod es, bipolar or monopolar-like psychotic disorders, coalescent lesions of the white matter, and well delineated lesions of the basal ganglia; and stage III over 60 years with subcortical dementia, pseudobulbar p alsy, diffuse leukoencephalopathy, and multiple well delineated lesion s of the basal ganglia. This phenotype differs from the other two prev iously described by high frequency of migraine, frequency of psychotic disorders, and early neurological manifestations. The new acronym ''c erebral autosomal dominant arteriopathy with subcortical infarcts, leu koencephalopathy, and migraine'' (CADASILM) is proposed to better desc ribe this particular subvariety of CADASIL.