Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort: The Use of Genetic Testing in Risk Stratification
van der Meulen, Marijke H; Herkert, Johanna C; den Boer, Susanna L; du Marchie Sarvaas, Gideon J; Blom, Nico; Ten Harkel, Arend D J; Breur, Hans M P J; Rammeloo, Lukas A J; Tanke, Ronald; Marcelis, Carlo; van de Laar, Ingrid M B H; Verhagen, Judith M A; Lekanne Dit Deprez, Ronald H; Barge-Schaapveld, Daniela Q C M; Baas, Annette; Sammani, Arjan; Christiaans, Imke; van Tintelen, J Peter; Dalinghaus, Michiel
(2022) Circulation. Genomic and precision medicine, volume 15, issue 5, pp. 375 - 385
(Article)
Abstract
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
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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.
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Keywords: Cardiomyopathy, Dilated/diagnosis, Genetic Association Studies, Genetic Testing, Humans, Myocarditis/genetics, Risk Assessment, cardiomyopathy, dilated, genetic testing, pediatric cardiology, Cardiology and Cardiovascular Medicine, Genetics(clinical), Genetics, Observational Study, Multicenter Study, Journal Article
ISSN: 2574-8300
Publisher: Lippincott Williams and Wilkins Ltd.
Note: Funding Information: MH van der Meulen was supported by a joint grant from “Stichting Hartedroom” [Rotterdam, the Netherlands] and the “Netherlands Heart Foundation” (2013T087). JP van Tintelen and M Dalinghaus acknowledge the support from the Netherlands Cardiovascular Research Initiative, an initiative with support of the Dutch Heart Foundation (CVON2014-40 DOSIS; CVON2020B005 DOUBLE-DOSE). Publisher Copyright: © 2022 Lippincott Williams and Wilkins. All rights reserved.
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