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The next step toward personalized recommendations for genetic cardiomyopathies

European Journal of Human Genetics volume 31, pages 1201–1203 (2023)Cite this article

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The Original Article was published on 10 April 2023

The genetic basis of dilated cardiomyopathy (DCM) is very heterogeneous, with over 65 genes described in association with its development. The most prevalent genetic etiology are truncating variants in TTN (TTNtv), that comprise around 50% of all genetic cases. Truncating variants in FLNC (FLNCtv) are the latest discovery to the genetic landscape of DCM, and the gene is now included in every cardiomyopathy gene panel. Despite being the ‘new kid on the block’, FLNCtv are already included in the latest guidelines of the European Society of Cardiology (ESC) as a significant risk factor for life-threatening arrhythmias, thereby guiding decision-making whether a patient with DCM requires an implantable cardioverter-defibrillator (ICD) [1]. This reflects the continuing advancements in cardiogenetics, and a concomitant shift toward more implications of genetic testing on clinical care.

In this issue of EJHG, Jacobs et al. compared clinical and MRI features of cardiomyopathy patients with a truncating variant in TTN (TTNtv) or FLNC (FLNCtv) [2]. TTNtv and FLNCtv are the most common genetic etiologies of cardiomyopathy, which can lead to heart failure, heart transplantation, and sudden cardiac death. Pathogenic truncating variants in these genes are linked to a broad spectrum of clinical cardiomyopathy phenotypes, including dilated cardiomyopathy (DCM), which is marked by left ventricular dysfunction, as well as arrhythmogenic cardiomyopathy (ACM), which is characterized by malignant ventricular arrhythmias and ventricular dysfunction. Furthermore, TTNtv and FLNCtv exhibit varying degrees of disease expressivity and incomplete penetrance. Therefore, the identification of a TTNtv or FLNCtv has significant implications for clinical practice when detected in a cardiomyopathy patient. Asymptomatic family members who carry the same variant are recommended to undergo yearly cardiac screening by electrocardiogram (ECG) and echocardiography, however, it remains unknown if this is necessary for every family member, and if the diagnostic tools are appropriate to detect cardiac disease associated with TTNtv or FLNCtv.

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Fig. 1: Truncating variants in TTN and FLNC are the most prevalent causes of dilated or arrhythmogenic cardiomyopathy.

References

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Funding

Funding

JAJV is supported by a research grant (Dekker – Clinical Scientist) from the Dutch Heart Foundation.

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Authors and Affiliations

  1. Department of Cardiology, Cardiovascular Research Institute Maastricht (CARIM), Maastricht Univeristy, Maastricht, the Netherlands

    Sophie L. V. M. Stroeks & Job A. J. Verdonschot

  2. European Reference Network for Rare, Low Prevalence and Complex Diseases of the Heart (ERN GUARD-Heart), Maastricht, the Netherlands

    Sophie L. V. M. Stroeks & Job A. J. Verdonschot

  3. Department of Cardiovascular Sciences, Katholieke Universiteit Leuven (KU Leuven), Leuven, Belgium

    Sophie L. V. M. Stroeks

  4. Department of Clinical Genetics, Maastricht University Medical Center (MUMC), Maastricht, the Netherlands

    Sophie L. V. M. Stroeks & Job A. J. Verdonschot

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  1. Sophie L. V. M. Stroeks
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  2. Job A. J. Verdonschot
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SLVMS and JAJV both wrote the comment equally. SLVMS designed and created the figure.

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Correspondence to Job A. J. Verdonschot.

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Stroeks, S.L.V.M., Verdonschot, J.A.J. The next step toward personalized recommendations for genetic cardiomyopathies. Eur J Hum Genet 31, 1201–1203 (2023). https://doi.org/10.1038/s41431-023-01394-w

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