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Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy
BACKGROUND: A genetic cause can be identified in 30% of noncompaction cardiomyopathy patients (NCCM) with clinical features ranging from asymptomatic cardiomyopathy to heart failure with major adverse cardiac events (MACE). METHODS AND RESULTS: To investigate genotype‐phenotype correlations, the gen...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912966/ https://www.ncbi.nlm.nih.gov/pubmed/31771441 http://dx.doi.org/10.1161/JAHA.119.012993 |
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author | van Waning, Jaap I. Moesker, Joost Heijsman, Daphne Boersma, Eric Majoor‐Krakauer, Danielle |
author_facet | van Waning, Jaap I. Moesker, Joost Heijsman, Daphne Boersma, Eric Majoor‐Krakauer, Danielle |
author_sort | van Waning, Jaap I. |
collection | PubMed |
description | BACKGROUND: A genetic cause can be identified in 30% of noncompaction cardiomyopathy patients (NCCM) with clinical features ranging from asymptomatic cardiomyopathy to heart failure with major adverse cardiac events (MACE). METHODS AND RESULTS: To investigate genotype‐phenotype correlations, the genotypes and clinical features of genetic NCCM patients were collected from the literature. We compared age at diagnosis, cardiac features and risk for MACE according to mode of inheritance and molecular effects for defects in the most common sarcomere genes and NCCM subtypes. Geno‐ and phenotypes of 561 NCCM patients from 172 studies showed increased risk in children for congenital heart defects (P<0.001) and MACE (P<0.001). In adult NCCM patients the main causes were single missense mutations in sarcomere genes. Children more frequently had an X‐linked or mitochondrial inherited defect (P=0.001) or chromosomal anomalies (P<0.001). MYH7 was involved in 48% of the sarcomere gene mutations. MYH7 and ACTC1 mutations had lower risk for MACE than MYBPC3 and TTN (P=0.001). The NCCM/dilated cardiomyopathy cardiac phenotype was the most frequent subtype (56%; P=0.022) and was associated with an increased risk for MACE and high risk for left ventricular systolic dysfunction (<0.001). In multivariate binary logistic regression analysis MYBPC3,TTN, arrhythmia ‐, non‐sarcomere non‐arrhythmia cardiomyopathy—and X‐linked genes were genetic predictors for MACE. CONCLUSIONS: Sarcomere gene mutations were the most common cause in adult patients with lower risk of MACE. Children had multi‐systemic disorders with severe outcome, suggesting that the diagnostic and clinical approaches should be adjusted to age at presentation. The observed genotype‐phenotype correlations endorsed that DNA diagnostics for NCCM is important for clinical management and counseling of patients. |
format | Online Article Text |
id | pubmed-6912966 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-69129662019-12-23 Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy van Waning, Jaap I. Moesker, Joost Heijsman, Daphne Boersma, Eric Majoor‐Krakauer, Danielle J Am Heart Assoc Systematic Review and Meta‐analysis BACKGROUND: A genetic cause can be identified in 30% of noncompaction cardiomyopathy patients (NCCM) with clinical features ranging from asymptomatic cardiomyopathy to heart failure with major adverse cardiac events (MACE). METHODS AND RESULTS: To investigate genotype‐phenotype correlations, the genotypes and clinical features of genetic NCCM patients were collected from the literature. We compared age at diagnosis, cardiac features and risk for MACE according to mode of inheritance and molecular effects for defects in the most common sarcomere genes and NCCM subtypes. Geno‐ and phenotypes of 561 NCCM patients from 172 studies showed increased risk in children for congenital heart defects (P<0.001) and MACE (P<0.001). In adult NCCM patients the main causes were single missense mutations in sarcomere genes. Children more frequently had an X‐linked or mitochondrial inherited defect (P=0.001) or chromosomal anomalies (P<0.001). MYH7 was involved in 48% of the sarcomere gene mutations. MYH7 and ACTC1 mutations had lower risk for MACE than MYBPC3 and TTN (P=0.001). The NCCM/dilated cardiomyopathy cardiac phenotype was the most frequent subtype (56%; P=0.022) and was associated with an increased risk for MACE and high risk for left ventricular systolic dysfunction (<0.001). In multivariate binary logistic regression analysis MYBPC3,TTN, arrhythmia ‐, non‐sarcomere non‐arrhythmia cardiomyopathy—and X‐linked genes were genetic predictors for MACE. CONCLUSIONS: Sarcomere gene mutations were the most common cause in adult patients with lower risk of MACE. Children had multi‐systemic disorders with severe outcome, suggesting that the diagnostic and clinical approaches should be adjusted to age at presentation. The observed genotype‐phenotype correlations endorsed that DNA diagnostics for NCCM is important for clinical management and counseling of patients. John Wiley and Sons Inc. 2019-11-27 /pmc/articles/PMC6912966/ /pubmed/31771441 http://dx.doi.org/10.1161/JAHA.119.012993 Text en © 2019 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made. |
spellingShingle | Systematic Review and Meta‐analysis van Waning, Jaap I. Moesker, Joost Heijsman, Daphne Boersma, Eric Majoor‐Krakauer, Danielle Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title | Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title_full | Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title_fullStr | Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title_full_unstemmed | Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title_short | Systematic Review of Genotype‐Phenotype Correlations in Noncompaction Cardiomyopathy |
title_sort | systematic review of genotype‐phenotype correlations in noncompaction cardiomyopathy |
topic | Systematic Review and Meta‐analysis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912966/ https://www.ncbi.nlm.nih.gov/pubmed/31771441 http://dx.doi.org/10.1161/JAHA.119.012993 |
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