Zusammenfassung
Die dilatative Kardiomyopathie (DCM) ist eine Erkrankung des Myokards heterogener Ätiologie. In bis zu 50% der Fälle wird eine familiäre Häufung beobachtet. In der letzten Dekade konnte eine Reihe von für die DCM ursächlichen Mutationen aufgeklärt werden. Hierbei handelt es sich um Mutationen in sarkomerischen Proteinen, aber auch in Proteinen der Zellmembran, des Zytoskeletts und des Zellkerns. Einer speziellen Komponente des Sarkomers, der Z-Scheibe, scheint dabei eine besondere Rolle in der Pathogenese zuzukommen. Zusätzlich zu den monogenetischen Ursachen einer DCM ist aber auch der „genetische Background“ von Bedeutung, da dieser über die endogenen Kompensationsmöglichkeiten den individuellen Krankheitsverlauf mitbestimmt. Bei genetisch bedingter Kardiomyopathie sollte immer auch eine Familienanamnese erhoben werden. Bei positiver Familienanamnese werden Angehörige 1. Grades zudem einem einfachen Screening mittels EKG und Echokardiographie unterzogen, um so ggf. weitere Betroffene zu identifizieren und frühzeitig behandeln zu können. Ferner sollte bei den genetischen Formen der Kardiomyopathie auch an extrakardiale Manifestationen, z. B. eine Beteiligung der Skelettmuskulatur gedacht werden. Die Aufklärung der verantwortlichen Krankheitsgene und molekularen Signalwege sollte es künftig ermöglichen, spezifische Therapiekonzepte zu entwickeln.
Abstract
Dilated cardiomyopathy is a disease of heterogenous etiology. In up to 50% of cases, familial aggregation is observed. During the past decade, several DCM-causing mutations could be identified, several of these in sarcomeric proteins. A specific component of the sarcomere, the z-disc, appears to be a “hot spot” in the molecular pathogenesis of DCM. Yet, mutations in proteins of the sarcolemma, the cytoskeleton, as well as the nuclear membrane can also lead to dilated cardiomyopathy. Morever, in addition to the monogenetic causes of cardiomyopathy, the genetic background of the individual patient may critically determine disease progression and the response to therapy. In the initial clinical evaluation of a patient newly diagnosed with DCM, it is important to obtain a careful family history in order to detect and treat additional family members which may be affected. Moreover, extracardiac manifestations of genetic DCM, such as skeletal muscle involvement, should be excluded. We anticipate that the elucidation of additional DCM disease genes as well as the underlying molecular pathways should lead to the development of novel specific therapies in the future.
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Danksagung
Wir danken Mark Lüdde, Christian Kuhn und Stefanie Lehrke für die Hilfe bei der Erstellung dieses Manuskripts.
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Frey, N., Katus, H. Die dilatative Kardiomyopathie als genetische Erkrankung. Internist 49, 43–50 (2008). https://doi.org/10.1007/s00108-007-1984-9
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DOI: https://doi.org/10.1007/s00108-007-1984-9