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Heart failure and cardiomyopathies
Potential genetic predisposition for anthracycline-associated cardiomyopathy in families with dilated cardiomyopathy
  1. Marijke Wasielewski1,
  2. Karin Y van Spaendonck-Zwarts1,2,
  3. Nico-Derk L Westerink1,
  4. Jan D H Jongbloed1,
  5. Aleida Postma3,
  6. Jourik A Gietema4,
  7. J Peter van Tintelen1 and
  8. Maarten P van den Berg5
  1. 1Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  2. 2Department of Clinical Genetics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  3. 3Department of Paediatric Oncology, University Medical Center Groningen, University of Groningen, Beatrix Children's Hospital, Groningen, The Netherlands
  4. 4Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  5. 5Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
  1. Correspondence to Dr Karin Y van Spaendonck-Zwarts; k.y.vanspaendonck{at}amc.nl

Abstract

Objective Anthracyclines are successfully used in cancer treatment, but their use is limited by their cardiotoxic side effects. Several risk factors for anthracycline-associated cardiomyopathy (AACM) are known, yet the occurrence of AACM in the absence of these known risk factors suggests that other factors must play a role. The purpose of this study was to evaluate whether a genetic predisposition for dilated cardiomyopathy (DCM) could be a potential risk factor for AACM.

Methods A hospital-based registry of 162 DCM families and two hospital-based registries of patients with cancer treated with systemic cancer therapy (n>6000) were reviewed focusing on AACM. Selected patients with AACM/DCM families with possible AACM (n=21) were analysed for mutations in cardiomyopathy-associated genes and presymptomatic cardiological evaluation of first-degree relatives was performed.

Results We identified five DCM families with AACM and one patient with AACM with a family member with a possible early sign of mild DCM. Pathogenic MYH7 mutations were identified in two of these six families. The MYH7 c.1633G>A (p.Asp545Asn) and c.2863G>A (p.Asp955Asn) mutations (one double mutant allele) were identified in a DCM family with AACM. The MYH7 c.4125T>A (p.Tyr1375X) mutation was identified in one patient with AACM.

Conclusions This study further extends the hypothesis that a genetic predisposition to DCM could be a potential risk factor for AACM.

  • GENETICS

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/

https://doi.org/10.1136/openhrt-2014-000116

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