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Fortschritt in der Pathogenese des Marfan-Syndroms und verwandter Krankheiten

Von der Klinik zum Labor und zurück

New insights in the pathogenesis of Marfan syndrome and related disorders

From clinic to bench to clinic

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medizinische genetik

Zusammenfassung

Hereditäre Erkrankungen des Bindegewebes bilden eine heterogene Gruppe von Krankheiten, die auf einer gestörten extrazellulären Matrix beruhen. Ein ausgeprägtes kardiovaskuläres Risiko begleitet viele dieser Krankheiten und führt zu erhöhter Morbidität und Mortalität im Kindes- und im Erwachsenenalter. Marfan-Syndrom und verwandte Erkrankungen gehören zu den wichtigsten Beispielen von Bindegewebskrankheiten mit kardiovaskulären Manifestationen. Insbesondere die fortschreitende Dilatation der Aortenwurzel resultiert in Aortenaneurysma und -dissektion, die oft einen vorzeitigen Tod zur Folge haben. Fortschritte in der klinischen molekularen Forschung während der letzten 10 Jahre haben das vorherrschende Konzept dieser Syndrome als Strukturdefekte des Bindegewebes in Krankheiten mit gestörten Zytokinsignalwegen mit einem breiten Spektrum von Entwicklungsanomalien erweitert. Neue Einsichten haben neue unerwartete Ziele für Ansätze von kausalen Therapien aller Aneurysmasyndrome geschaffen, auch für die häufigen, nicht syndromalen Aneurysmaformen.

Abstract

Heritable connective tissue disorders comprise a heterogeneous group of disorders that result from genetic defects affecting normal extracellular matrix assembly. Many of these diseases are associated with a significant cardiovascular risk leading to morbidity and mortality in childhood or young adulthood. Prime examples that represent important genetic models for cardiovascular pathology are the Marfan syndrome and related disorders. In these conditions, progressive dilatation of the aortic root leads to aortic dissection, often associated with precocious death. Over the last decade tremendous progress in clinical and molecular research has changed the prevailing concept of these syndromes as structural disorders of the connective tissue into diseases manifesting perturbed cytokine signaling with widespread developmental abnormalities. These insights opened new and unexpected targets for causally directed drug treatments for these aneurysm syndromes, and by extent, also for the more common non-syndromic forms of aneurysm formation, a major cause of morbidity and mortality in the Western world.

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Authors and Affiliations

  1. Ghent University Hospital, Center for Medical Genetics, De Pintelaan 185, B-9000, Ghent, Belgien

    B.L. Callewaert & A.M. De Paepe

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  1. B.L. Callewaert
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  2. A.M. De Paepe
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Correspondence to B.L. Callewaert.

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B.C. ist ein Research Fellow der Fund for Scientific Research Belgium, unterstützt durch Projekt 3G009406 der FWO Flandern an A. de Paepe und durch GOA Projekt G12051203 der Universität Ghent.

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Callewaert, B., De Paepe, A. Fortschritt in der Pathogenese des Marfan-Syndroms und verwandter Krankheiten. medgen 20, 6–17 (2008). https://doi.org/10.1007/s11825-008-0090-2

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