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Genetic diagnostics of inherited aortic diseases

Medical strategy analysis

Genetische Diagnostik von erblichen Aortenerkrankungen

Medizinische Strategieanalyse

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Abstract

Genetic aortic syndromes (GAS) include Marfan, Loeys–Dietz, vascular Ehlers–Danlos, and Turner syndrome as well as congenital bicuspid aortic valve. The clinical management of these diseases has certain similarities and differences. We employed medical strategy analysis to test the utility of genetic diagnostics in the management of GAS. We chose the standpoint of the cardiologist for our analysis. In the first step, the medical goals in the management of GAS are specified. In the second step, the accuracy of genetic diagnostics for GAS is examined. Finally, conclusions can be drawn about the utility of genetic diagnostics in managing GAS. We found that genetic diagnostics is necessary to exclude GAS, to diagnose GAS, and to specify disease types. Second, combining phenotype with genotype information maximizes the predictability of the course of disease. Third, with genetic diagnostics it is possible to predict the birth of children with causative mutations for GAS and to initiate drug therapy to prevent the onset of aortic dilatation or to slow down its progression to aortic aneurysm. Finally, genetic diagnostics improves prognostic predictions and thereby contributes to a better timing of elective surgery and to a better choice of procedures. The findings of our medical strategy analysis indicate the high utility of genetic diagnostics for managing GAS.

Zusammenfassung

Genetische Aortensyndrome (GAS) umfassen das Marfan‑, Loeys-Dietz-, vaskuläre Ehlers-Danlos- und Turner-Syndrom sowie die kongenital bikuspide Aortenklappe. Das klinische Management dieser Erkrankungen weist Ähnlichkeiten und Unterschiede auf. Die Autoren verwendeten die medizinische Strategieanalyse, um die Nützlichkeit der genetischen Diagnostik zur Umsetzung der medizinischen Behandlungsziele beim Management von GAS zu ermitteln. Als Basis der Analyse wurde der Standpunkt des Kardiologen gewählt. Im ersten Schritt wurden die medizinischen Ziele des Managements von GAS spezifiziert. Im zweiten Schritt untersuchten die Autoren die diagnostische Genauigkeit der genetischen Diagnostik. Im dritten Schritt wurden Schlüsse auf die Nützlichkeit der Gendiagnostik zum Management von GAS gezogen. Als Ergebnis stellte sich heraus, dass erstens die genetische Diagnostik notwendig ist, um GAS auszuschließen oder zu diagnostizieren und um die vorliegende Erkrankung zu spezifizieren. Zweitens erhöht die genetische Diagnostik die Vorhersagbarkeit des Verlaufs einer Aortenerkrankung. Drittens macht es die genetische Diagnostik möglich, die Geburt von Kindern mit GAS-bedingenden Mutationen vorherzusagen und eine prophylaktische Medikation zur Verhinderung der Dilatation oder der Bildung von Aneurysmen der Aorta einzuleiten. Schließlich erwirkt die genetische Diagnostik durch bessere Prognosen ein verbessertes Timing prophylaktischer Operationen und trägt zur verbesserten Auswahl spezifischer Prozeduren bei. Damit folgt aus der medizinischen Strategieanalyse, dass die genetische Diagnostik einen großen Nutzen beim Management von GAS aufweist.

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Authors and Affiliations

  1. Centre of Cardiology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    Y. von Kodolitsch

  2. Deutsches Aortenzentrum Hamburg (DAZH), Zentrum für Kardiologie und kardiovaskuläre Chirurgie, Universitätsklinikum Hamburg Eppendorf, Martinistrasse 52, 20246, Hamburg, Germany

    Y. von Kodolitsch

  3. Institute of Human Genetics, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

    K. Kutsche

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Y. von Kodolitsch and K. Kutsche declare that they have no competing interests.

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von Kodolitsch, Y., Kutsche, K. Genetic diagnostics of inherited aortic diseases. Herz 42, 459–467 (2017). https://doi.org/10.1007/s00059-017-4577-y

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