CADASIL in central Italy: a retrospective clinical and genetic study in 229 patients.

[cadasil]

The objective of the study is to detail clinical and NOTCH 3 gene mutational spectrum in a large group of Italian CADASIL patients . Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL ) is a familial cerebral small vessels disease caused by mutations in the NOTCH 3 gene on 19 p 13 usually presenting in young or middle adulthood . Characteristic features include migraine , recurrent lacunar stroke , subcortical dementia , mood disturbances and leukoencephalopathy . The disorder is often overlooked and misdiagnosed . CADASIL prevalence and disease burden is still undetermined . We retrospectively reviewed demographic , clinical , and mutational characteristic of all CADASIL patients diagnosed from January 2002 to December 2012 in three referral centers for neurogenetic and cerebrovascular diseases in central Italy . 229 NOTCH 3 positive subjects were identified . Mean age at diagnosis was 57 .8 ± 14 .7 years , and 48 .6 ± 17 .1 years at first symptom onset . Most frequent clinical symptoms were ischemic events (59 %) and psychiatric disturbances (48 %). The highest percentage of mutations were found on exons 4 and 19 (20 .6 and 17 .6 % respectively ), the remaining being dispersed over the entire EGF -like region of the NOTCH 3 gene . 209 patients resided in a circumscribed geographic area which included three regions of the central Italy , yielding a minimum prevalence of 4 .1 per 100 .000 adult inhabitants . This is the most extensive study on CADASIL in Italy . Clinical phenotype showed several peculiarities in frequency and presentation of the main disease manifestations . Our study enlarges the number of pathogenic NOTCH 3 mutations and due to the heterogeneous mutational spectrum observed suggests that full sequencing of exons 2 -24 is mandatory for CADASIL screening in the Italian population .