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Klinik und Genetik der hypertrophen und dilatativen Kardiomyopathie

Clinical and genetic aspects of hypertrophic and dilated cardiomyopathy

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Zusammenfassung

Primäre Kardiomyopathien sind mit einer geschätzten Prävalenz von 0,3–0,4% in der Bevölkerung keine seltenen Erkrankungen. Sie gehören zu den häufigsten Ursachen der systolischen Herzinsuffizienz und des plötzlichen Herztods bei unter 35-Jährigen. Durch molekulargenetische Untersuchungen konnten bis heute 49 Krankheitsgene der hypertrophen und dilatativen Kardiomyopathie identifiziert werden, wobei häufig Proteine des Sarkomers, der kardialen Z-Scheibe und des Zytoskeletts betroffen sind. Durch neue genetische Analyseverfahren, die auf dem „next generation sequencing“ basieren, ist es nun erstmals möglich, die Vielzahl bekannter Krankheitsgene umfassend zu untersuchen.

Auf die Diagnosestellung einer Kardiomyopathie bei einem Indexpatienten sollte immer eine klinische Untersuchung der Familie folgen, um frühzeitig erkrankte Familienmitglieder erkennen und einer kardiologischen Betreuung zuführen zu können. Durch eine genetische Testung in der Familie des Indexpatienten ist eine Identifikation von Mutationsträgern mit bis zu diesem Zeitpunkt unauffälligem klinischem Phänotyp möglich. Die genetische Charakterisierung erleichtert weiterhin die Differenzialdiagnose und Risikostratifizierung der betroffenen Patienten.

Abstract

Primary cardiomyopathies are frequent heart diseases with an estimated prevalence of 0.3–0.4% in the general population, significantly contributing to systolic heart failure and sudden cardiac death in the young. Molecular genetic studies have identified 49 different disease genes for hypertrophic and dilated cardiomyopathy, often involving proteins of the sarcomere, the cardiac Z-disc and the cytoskeleton. With the development of new, advanced technologies based on next-generation sequencing, it is now possible to efficiently screen all known disease genes in an individual patient.

The clinical workup of cardiomyopathies should always include the investigation of the patient’s family to account for the familial aggregation of cardiomyopathies and identify diseased as well as asymptomatic carriers of mutations. The detection of specific genotypes facilitates diagnostic classification and can improve risk stratification in affected patients.

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Danksagung

Für die Unterstützung unserer Kardiomyopathieforschung danken wir dem Bundesministerium für Bildung und Forschung [NGFN-plus 01GS0836, NGFN-transfer 01GR0823, Deutsches Herzforschungszentrum (DZHK)], der Europäischen Union (FP7 INHERITANCE und INSIGHT DCM) und der Universität Heidelberg (Innovationsfond FRONTIER). Wir danken weiterhin Dr. Sebastian Greiner, Dr. Henning Steen und Dipl.-Biol. Jan Haas für ihre Mithilfe bei der Erstellung von Abbildungen.

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  1. Abteilung Innere Medizin III (Schwerpunkt Kardiologie, Angiologie und Pneumologie), Universitätsklinikum Heidelberg, Im Neuenheimer Feld 410, 69120, Heidelberg, Deutschland

    B. Meder &  H.A. Katus

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  2. H.A. Katus
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Correspondence to H.A. Katus.

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Meder, B., Katus, H. Klinik und Genetik der hypertrophen und dilatativen Kardiomyopathie. Internist 53, 408–418 (2012). https://doi.org/10.1007/s00108-011-2988-z

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