TY - JOUR
T1 - Genetic Evaluation of A Nation-Wide Dutch Pediatric DCM Cohort
T2 - The Use of Genetic Testing in Risk Stratification
AU - van der Meulen, Marijke H.
AU - Herkert, Johanna C.
AU - den Boer, Susanna L.
AU - du Marchie Sarvaas, Gideon J.
AU - Blom, Nico A.
AU - Ten Harkel, Arend D.J.
AU - Breur, Hans M.P.J.
AU - Rammeloo, Lukas A.J.
AU - Tanke, Ronald B.
AU - Marcelis, Carlo
AU - van de Laar, Ingrid M.B.H.
AU - Verhagen, Judith M.A.
AU - Lekanne Dit Deprez, Ronald H.
AU - Barge-Schaapveld, Daniela Q.C.M.
AU - Baas, Annette F.
AU - Sammani, Arjan
AU - Christiaans, Imke
AU - van Tintelen, J. Peter
AU - Dalinghaus, Michiel
PY - 2022/10/1
Y1 - 2022/10/1
N2 - 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.
AB - 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.
KW - cardiomyopathy, dilated
KW - genetic testing
KW - pediatric cardiology
U2 - 10.1161/CIRCGEN.120.002981
DO - 10.1161/CIRCGEN.120.002981
M3 - Article
C2 - 36178741
AN - SCOPUS:85140273544
SN - 2574-8300
VL - 15
JO - Circulation. Genomic and precision medicine
JF - Circulation. Genomic and precision medicine
IS - 5
M1 - e002981
ER -