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Canadian Journal of Cardiology

The Expanding Clinical Spectrum of Extracardiovascular and Cardiovascular Manifestations of Heritable Thoracic Aortic Aneurysm and Dissection

  • Timothy J. Bradley
    Correspondence
    Corresponding author: Dr Timothy J. Bradley, The Labatt Family Heart Centre, The Hospital for Sick Children, 555 University Ave, Toronto, Ontario M5G 1X8, Canada. Tel.: +1-416-813-7610; fax: +1-416-813-7547.
    Affiliations
    Division of Cardiology, Department of Paediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Sarah C. Bowdin
    Affiliations
    Division of Cardiology, Department of Paediatrics, The Labatt Family Heart Centre, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada

    Division of Clinical and Metabolic Genetics, Department of Paediatrics, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada
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  • Chantal F.J. Morel
    Affiliations
    Fred A. Litwin Family Center in Genetic Medicine, Department of Medicine, University Health Network and Mount Sinai Hospital, University of Toronto, Toronto, Ontario, Canada
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  • Reed E. Pyeritz
    Affiliations
    Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA
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Published:November 13, 2015DOI:https://doi.org/10.1016/j.cjca.2015.11.007

      Abstract

      More than 30 heritable conditions are associated with thoracic aortic aneurysm and dissection (TAAD). Heritable syndromic conditions, such as Marfan syndrome, Loeys-Dietz syndrome, and vascular Ehlers-Danlos syndrome, have somewhat overlapping systemic features, but careful clinical assessment usually enables a diagnosis that can be validated with genetic testing. Nonsyndromic FTAAD can also occur and in 20%-25% of these probands mutations exist in genes that encode elements of the extracellular matrix, signalling pathways (especially involving transforming growth factor-β), and vascular smooth muscle cytoskeletal and contractile processes. Affected individuals with either a syndromic presentation or isolated TAAD can have mutations in the same gene. In this review we focus on the genes currently known to have causal mutations for syndromic and isolated FTAAD and outline the range of associated extracardiovascular and cardiovascular manifestations with each.

      Résumé

      Plus de 30 affections héréditaires sont associées à l’anévrisme et à la dissection de l’aorte thoracique (TAAD : thoracic aortic aneurysm and dissection). Les affections héréditaires syndromiques, comme le syndrome de Marfan, le syndrome de Loeys-Dietz et la forme vasculaire du syndrome d’Ehlers-Danlos, présentent des caractéristiques systémiques qui se recoupent quelque peu, mais une évaluation clinique consciencieuse permet habituellement de poser un diagnostic qui peut être validé par dépistage génétique. La forme familiale non syndromique de TAAD peut également apparaître, et 20 % à 25 % des mutations chez les proposants existent dans les gènes qui encodent les éléments de la matrice extracellulaire, les voies de signalisation (impliquant particulièrement le facteur de croissance transformant β [TGF-β : transforming growth factor β]) et les processus cytosquelettiques et contractiles des muscles lisses vasculaires. Les individus qui présentent soit le tableau clinique d’un syndrome ou un TAAD isolé peuvent avoir des mutations dans le même gène. Dans cette revue, nous nous concentrons sur les gènes actuellement connus comme étant porteurs de mutations causales de TAAD familial syndromique et isolé, et exposons les grandes lignes des diverses manifestations cardiovasculaires et extracardiovasculaires associées à chacune.
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