P-16

A portuguese family with CADASIL diagnosis with anticipation age of onset observed

Maria Lopes-de-Almeida^I; Lina Ramos^I; Gustavo Cordeiro^II; Rosário Almeida^III; Joaquim Sá^I; Jorge M Saraiva^II,IV

^IMedical Genetics Unit, Hospital Pediátrico, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
^IINeurology Unit, Hospital Universitário de Coimbra, Centro Hospitalar e Universitário de Coimbra, Coimbra, Portugal;
^IIICenter of Neuroscience and Cell Biology, Faculty of Medicine, University of Coimbra, Portugal; ]]> ^IVUniversity Clinic of Pediatrics, Faculty of Medicine, University of Coimbra, Portugal

marialopesdealmeida@chc.min-saude.pt

Introdution: Cerebral Autossomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a rare hereditary disease characterized by recurrent transient ischemic attacks, strokes, and vascular dementia.

Since it is a dominant disease, heterozygous and homozygous patients are expected to be clinically indistinguishable. Nevertheless, some homozygous patients with CADASIL have been reported and in some cases with a severe phenotype.

Case report: We would like to report a Portuguese family with inbreeding with diagnosis of CADASIL. It has been found the p.Arg558Cys mutation in NOTCH3 gene in six members of this family studied, two of them in homozygosity. One of the homozygous case  present a more severe phenotype compared with his relatives with an age of onset at 10 years old. According to this finding, we wonder if the homozygosity can justify this early age of onset case or its severity.

Discussion: Differences in clinical profile between homozygous and heterozygous of this family  members and between other CADASIL families with homozygosity described should be discuss in order to understand if the homozygosity state increases the pathologic consequences of the mutation providing a more severe and early phenotype.