PhD defence Sophie Stroeks

Keywords: Dilated cardiomyopathy (DCM), Genetic testing, Sex differences, Personalized cardiology

"The Genetic Landscape of Dilated Cardiomyopathy Interpretation, Penetrance, and Clinical Implications of Genetica Testing in the Eras of Precision Cardiology"

Dilated cardiomyopathy (DCM) is a common heart muscle disease, affecting about 1 in 250 people, and it can lead to heart failure and dangerous heart rhythm disorders. This thesis shows that genetic DCM affects men and women differently, and that these differences matter for diagnosis and long-term risk. By studying thousands of patients from the Maastricht region as well as international cohorts, the research reveals that women generally have a more favourable disease course, yet remain underrepresented in scientific studies. Men more often carry truncating variants in the TTN gene and tend to develop DCM at a younger age. In women, disease-causing variants are more frequently found in other genes, such as DSP and sarcomere-related genes. Importantly, men with genetic DCM, especially those with high-risk genotypes, have a worse long-term prognosis compared to women. These insights support the need to include sex as a key factor in risk prediction models, screening strategies, and follow-up. Overall, the findings strengthen a more personalised “genotype-first” approach, where genetic information guides care for patients and their families.

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