Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification

Marijke H. van der Meulen, Johanna C. Herkert, Susanna L. den Boer, Gideon J. du Marchie Sarvaas, Nico A. Blom, Arend D. J. ten Harkel, Hans M. P. J. Breur, Lukas A. J. Rammeloo, Ronald B. Tanke, Carlo Marcelis, Ingrid M. B. H. van de Laar, Judith M. A. Verhagen, Ronald H. Lekanne Dit Deprez, Daniela Q. C. M. Barge-Schaapveld, Annette F. Baas, Arjan Sammani, Imke Christiaans, J. Peter van Tintelen, Michiel Dalinghaus

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BACKGROUND: This study aimed to describe the current practice and results of genetic evaluation in Dutch children with dilated cardiomyopathy and to evaluate genotype-phenotype correlations that may guide prognosis. METHODS: We performed a multicenter observational study in children diagnosed with dilated cardiomyopathy, from 2010 to 2017. RESULTS: One hundred forty-four children were included. Initial diagnostic categories were idiopathic dilated cardiomyopathy in 67 children (47%), myocarditis in 23 (16%), neuromuscular in 7 (5%), familial in 18 (13%), inborn error of metabolism in 4 (3%), malformation syndrome in 2 (1%), and "other" in 23 (16%). Median follow-up time was 2.1 years [IQR 1.0-4.3]. Hundred-seven patients (74%) underwent genetic testing. We found a likely pathogenic or pathogenic variant in 38 children (36%), most often in MYH7 (n = 8). In 1 patient initially diagnosed with myocarditis, a pathogenic LMNA variant was found. During the study, 39 patients (27%) reached study endpoint (SE: all-cause death or heart transplantation). Patients with a likely pathogenic or pathogenic variant were more likely to reach SE compared with those without (hazard ratio 2.8; 95% CI 1.3-5.8, P = 0.007), while transplant-free survival was significantly lower (P = 0.006). Clinical characteristics at diagnosis did not differ between the 2 groups. CONCLUSIONS: Genetic testing is a valuable tool for predicting prognosis in children with dilated cardiomyopathy, with carriers of a likely pathogenic or pathogenic variant having a worse prognosis overall. Genetic testing should be incorporated in clinical work-up of all children with dilated cardiomyopathy regardless of presumed disease pathogenesis.
Original languageEnglish
Pages (from-to)375-385
Number of pages11
JournalCirculation. Genomic and precision medicine
Issue number5
Publication statusPublished - 1 Oct 2022


  • cardiomyopathy, dilated
  • genetic testing
  • pediatric cardiology

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