Family tree intertwined with a human heart, DNA strands, and cardiogram illustrating the intersection of genetics, family history, and cardiac health in understanding dilated cardiomyopathy.

Decoding DCM: How Genetic Testing Can Save Your Family's Hearts

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Beau Callahan in Health & Wellness August 2025 • 4 min read.

"Unraveling the complexities of dilated cardiomyopathy and the critical role of genetic screening in early detection and prevention."


In the ever-evolving landscape of cardiac health, genetic testing has emerged as a powerful tool in diagnosing and managing various cardiomyopathies. Among these, dilated cardiomyopathy (DCM) stands out as a condition where genetics play a significant role. Over the past decade, the identification of numerous genes associated with DCM has transformed how we approach this heart condition.

The cornerstone of genetic testing in DCM lies in its ability to trigger cascade screening within families. Once a class 4 (likely pathogenic) or class 5 (pathogenic) variant is identified in an individual, also known as the index patient, this discovery sets off a series of genetic screenings among family members. This process is not merely a test; it's a gateway to understanding risk and making informed healthcare decisions.

Interpreting the outcomes of genetic tests requires a collaborative effort involving geneticists, cardiologists, and the individuals and families affected. The results, which are probabilistic, can either reassure those who do not carry the pathogenic variant, or lead to tailored monitoring for those who do.

LMNA Gene: A Key Exception Where Genotype Guides Treatment

Family tree intertwined with a human heart, DNA strands, and cardiogram illustrating the intersection of genetics, family history, and cardiac health in understanding dilated cardiomyopathy.

While genotype typically doesn't dictate treatment in most genetic cardiomyopathies, the LMNA gene, encoding lamin A/C, presents a notable exception. Disease-associated LMNA variants are found in approximately 6% of DCM patients. These patients often exhibit a highly penetrant phenotype, including sinus node dysfunction, atrioventricular conduction disease, atrial fibrillation or flutter, DCM, and, in some instances, muscular dystrophy.

Early studies revealed high rates of sudden cardiac death in LMNA variant carriers with pacemakers for conduction disease, suggesting a tachyarrhythmic mode of death. Consequently, implantable cardioverter-defibrillators (ICDs) became a key intervention, effectively treating potentially lethal tachyarrhythmias in LMNA-positive patients needing pacemakers.

  • Male sex
  • Nonmissense mutation
  • Nonsustained ventricular tachycardias
  • Left ventricular ejection fraction <45%
These factors have proven to be strong indicators for poor outcomes and earlier disease presentation. Identifying these risk factors is crucial for timely intervention.
Adding to this body of knowledge, Cowan et al. have focused their research on the LMNA gene, as highlighted in a recent issue of Circulation Genomic and Precision Medicine. Their follow-up study of 19 pedigrees with apparent LMNA-related DCM revealed a fascinating twist: in six of these families, at least one individual diagnosed with idiopathic DCM did not carry the expected disease-causing LMNA variant.

Navigating the Complexities: A Call for Comprehensive Evaluation

The insights from studies like Cowan et al.'s underscore the necessity of moving beyond simplistic, monogenic models of disease. A thorough family history, detailed evaluation of all close relatives, and awareness of potential environmental influences are paramount. By considering the broader genetic and environmental landscape, healthcare professionals can provide more informed and effective care, ultimately safeguarding the heart health of families affected by DCM.

About this Article -

This article was crafted using a human-AI hybrid and collaborative approach. AI assisted our team with initial drafting, research insights, identifying key questions, and image generation. Our human editors guided topic selection, defined the angle, structured the content, ensured factual accuracy and relevance, refined the tone, and conducted thorough editing to deliver helpful, high-quality information.See our About page for more information.

This article is based on research published under:

DOI-LINK: 10.1161/circgen.118.002249, Alternate LINK

Title: Additional Genetic Variants In Inherited Dilated Cardiomyopathy

Subject: General Medicine

Journal: Circulation: Genomic and Precision Medicine

Publisher: Ovid Technologies (Wolters Kluwer Health)

Authors: J. Peter Van Tintelen, Yigal M. Pinto

Published: 2018-07-01

Everything You Need To Know

1

What is Dilated Cardiomyopathy (DCM)?

Dilated cardiomyopathy (DCM) is a heart condition where the heart's main pumping chamber (left ventricle) becomes enlarged (dilated) and cannot pump blood effectively. This can lead to heart failure, arrhythmias, and sudden cardiac death. Genetic testing plays a crucial role in identifying gene variants associated with DCM, allowing for early detection and intervention.

2

Why is genetic testing important for DCM?

Genetic testing is significant in DCM because it helps identify individuals and families at risk. When a pathogenic variant is found in an individual (the index patient), it triggers cascade screening, which involves testing family members. This allows for proactive monitoring and early intervention strategies, such as lifestyle changes, medications, or the use of implantable cardioverter-defibrillators (ICDs) to prevent sudden cardiac death, particularly in cases involving the LMNA gene.

3

How does the LMNA gene influence treatment for DCM?

The LMNA gene is a key exception where genotype influences treatment in DCM. Variants in the LMNA gene are associated with a highly penetrant phenotype, including sinus node dysfunction, atrioventricular conduction disease, atrial fibrillation or flutter, and muscular dystrophy. Individuals with LMNA variants often benefit from implantable cardioverter-defibrillators (ICDs) to manage potentially lethal tachyarrhythmias.

4

What is cascade screening in the context of DCM?

Cascade screening is the process of testing family members for a specific gene variant once it has been identified in an individual (the index patient). This involves offering genetic testing to relatives to determine if they carry the same variant. If a family member tests positive, they can undergo tailored monitoring and receive appropriate medical care. This approach is crucial in the management of DCM, as it allows for the early identification of at-risk individuals and the implementation of preventative measures.

5

What are some of the risk factors that can indicate poor outcomes in DCM?

Several factors, including male sex, nonmissense mutation, nonsustained ventricular tachycardias, and a left ventricular ejection fraction <45%, have been identified as indicators of poor outcomes and earlier disease presentation in individuals with DCM. Identifying these risk factors is crucial for timely intervention. These factors can help healthcare professionals assess an individual's risk and tailor their treatment plan accordingly, ultimately aiming to improve outcomes and prevent complications.

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