The role of NKX2-5 gene polymorphisms in congenital heart disease (CHD): a systematic review and meta-analysis

Abstract Background The gene NKX2-5 is a key transcription factor that plays an essential role in normal cardiac development. Although some recent studies have studied the role of polymorphisms in the NKX2-5 gene in congenital heart diseases (CHDs), the results were not consistent and remained uncertain. Therefore, we conduct a review of literature and investigate the association of genetic polymorphisms with CHDs. Results We selected seventeen studies regarding the association of NKX2-5 gene rs2277923 polymorphism with CHDs. Overall, in all the tested genetic models, the 63A > G polymorphism was not significantly associated with increased congenital heart defects risk. We used pooled odds ratios (OR) to calculate the association of CHDs with rs2277923 including allelic model: OR 1.00, 95% CI 0.82–1.21; homozygote model: OR 0.95, 95%CI 0.68–1.33, recessive model: OR 0.89 CI 0.70–1.13, heterozygote model: OR: 1.09, 95%CI 0.87–1.37, dominant model: OR 1.08 CI 0.82–1.42 and overdominant model: OR 1.17 CI 1.01–1.35. In addition, our analysis suggests that no publication bias exists in this meta-analysis. Conclusions Our findings suggested that 63A > G polymorphism in the NKX2-5 gene was not significantly associated with congenital heart defects. However, in the future, more studies with increased sample size are required that may provide us more definite conclusions.

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POSTTRANSCRIPTIONAL REGULATION IN CONGENITAL HEART DISEASE: THE ROLE OF miRNA

Complex Issues of Cardiovascular Diseases ◽

10.17802/2306-1278-2019-8-3-85-95 ◽

2019 ◽

Vol 8 (3) ◽

pp. 85-95

Author(s):

A. V. Ponasenko ◽

A. V. Tsepokina

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart Defects ◽

Posttranscriptional Regulation ◽

Congenital Heart ◽

Heart Diseases ◽

Heart Defects ◽

Ecological Factors ◽

Fetal Abnormality

Congenital heart disease is the most common fetal abnormality resulting in high pediatric disability and mortality. Congenital heart disease is a heterogeneous group of cardiac abnormalities including atrial septal defect, valvular defects and cardiac outflow tract anomalies. Genetic, epigenetic and ecological factors leading to the development of congenital heart defects in each particular case remain poorly understood. Nevertheless, multifactorial and polygenic mechanisms underlying the disease may be suggested. Moreover, advanced genetic technologies including single nucleotide polymorphism testing, copy number variation and next-generation sequencing ensure early detection of genetic causes of heart abnormalities. Recent studies suggested the contributing role of small non-coding RNA (miRNA) in the pathogenesis of congenital heart defects. miRNA is known to coordinate the development of heart and stimulate such pathological processes like fibrosis, hypertrophy and impaired angiogenesis. Thus, the study of miRNA and its impact on the pathogenesis of various heart diseases has demonstrated its promising potential for therapeutic targets in regenerative medicine. The review presents recent genetic findings, miRNA functions, signaling pathways and evidences on its role in the development of certain congenital heart defects.

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Faculty Opinions recommendation of Pulse oximetry screening for critical congenital heart defects in asymptomatic newborn babies: a systematic review and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.717697909.793152973 ◽

2012 ◽

Author(s):

Willem Helbing

Keyword(s):

Systematic Review ◽

Pulse Oximetry ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Defects ◽

Meta Analysis ◽

Pulse Oximetry Screening

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Personalized Genetic Diagnosis of Congenital Heart Defects in Newborns

Journal of Personalized Medicine ◽

10.3390/jpm11060562 ◽

2021 ◽

Vol 11 (6) ◽

pp. 562

Author(s):

Olga María Diz ◽

Rocio Toro ◽

Sergi Cesar ◽

Olga Gomez ◽

Georgia Sarquella-Brugada ◽

...

Keyword(s):

Congenital Heart Disease ◽

Heart Disease ◽

Congenital Heart Defects ◽

Congenital Malformations ◽

Congenital Heart ◽

Heart Diseases ◽

Heart Defects ◽

Genetic Diagnosis ◽

Single Nucleotide Variants ◽

Personalized Approach

Congenital heart disease is a group of pathologies characterized by structural malformations of the heart or great vessels. These alterations occur during the embryonic period and are the most frequently observed severe congenital malformations, the main cause of neonatal mortality due to malformation, and the second most frequent congenital malformations overall after malformations of the central nervous system. The severity of different types of congenital heart disease varies depending on the combination of associated anatomical defects. The causes of these malformations are usually considered multifactorial, but genetic variants play a key role. Currently, use of high-throughput genetic technologies allows identification of pathogenic aneuploidies, deletions/duplications of large segments, as well as rare single nucleotide variants. The high incidence of congenital heart disease as well as the associated complications makes it necessary to establish a diagnosis as early as possible to adopt the most appropriate measures in a personalized approach. In this review, we provide an exhaustive update of the genetic bases of the most frequent congenital heart diseases as well as other syndromes associated with congenital heart defects, and how genetic data can be translated to clinical practice in a personalized approach.

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Children Born with Congenital Heart Defects and Growth Restriction at Birth: A Systematic Review and Meta-Analysis

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17093056 ◽

2020 ◽

Vol 17 (9) ◽

pp. 3056 ◽

Cited By ~ 1

Author(s):

Ali Ghanchi ◽

Neil Derridj ◽

Damien Bonnet ◽

Nathalie Bertille ◽

Laurent J. Salomon ◽

...

Keyword(s):

Systematic Review ◽

Congenital Heart Defects ◽

Gestational Age ◽

Small For Gestational Age ◽

Congenital Heart ◽

Heart Defects ◽

Data Extraction ◽

Meta Analysis ◽

Adverse Outcomes ◽

Growth Restriction

Newborns with congenital heart defects tend to have a higher risk of growth restriction, which can be an independent risk factor for adverse outcomes. To date, a systematic review of the relation between congenital heart defects (CHD) and growth restriction at birth, most commonly estimated by its imperfect proxy small for gestational age (SGA), has not been conducted. Objective: To conduct a systematic review and meta-analysis to estimate the proportion of children born with CHD that are small for gestational age (SGA). Methods: The search was carried out from inception until 31 March 2019 on Pubmed and Embase databases. Studies were screened and selected by two independent reviewers who used a predetermined data extraction form to obtain data from studies. Bias was assessed using the Critical Appraisal Skills Programme (CASP) checklist. The database search identified 1783 potentially relevant publications, of which 38 studies were found to be relevant to the study question. A total of 18 studies contained sufficient data for a meta-analysis, which was done using a random effects model. Results: The pooled proportion of SGA in all CHD was 20% (95% CI 16%–24%) and 14% (95% CI 13%–16%) for isolated CHD. Proportion of SGA varied across different CHD ranging from 30% (95% CI 24%–37%) for Tetralogy of Fallot to 12% (95% CI 7%–18%) for isolated atrial septal defect. The majority of studies included in the meta-analysis were population-based studies published after 2010. Conclusion: The overall proportion of SGA in all CHD was 2-fold higher whereas for isolated CHD, 1.4-fold higher than the expected proportion in the general population. Although few studies have looked at SGA for different subtypes of CHD, the observed variability of SGA by subtypes suggests that growth restriction at birth in CHD may be due to different pathophysiological mechanisms.

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Role of Ultrasonography in Early Gestation in the Diagnosis of Congenital Heart Defects

Journal of Ultrasound in Medicine ◽

10.7863/jum.2010.29.5.817 ◽

2010 ◽

Vol 29 (5) ◽

pp. 817-821 ◽

Cited By ~ 7

Author(s):

Reem S. Abu-Rustum ◽

Linda Daou ◽

Sameer E. Abu-Rustum

Keyword(s):

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Defects ◽

Early Gestation

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Drosophila Heart as a Model for Cardiac Development and Diseases

Cells ◽

10.3390/cells10113078 ◽

2021 ◽

Vol 10 (11) ◽

pp. 3078

Author(s):

Anissa Souidi ◽

Krzysztof Jagla

Keyword(s):

Cardiac Dysfunction ◽

Congenital Heart ◽

Cardiac Development ◽

Heart Diseases ◽

Heart Defects ◽

Fruit Fly ◽

Model System ◽

Fast Imaging

The Drosophila heart, also referred to as the dorsal vessel, pumps the insect blood, the hemolymph. The bilateral heart primordia develop from the most dorsally located mesodermal cells, migrate coordinately, and fuse to form the cardiac tube. Though much simpler, the fruit fly heart displays several developmental and functional similarities to the vertebrate heart and, as we discuss here, represents an attractive model system for dissecting mechanisms of cardiac aging and heart failure and identifying genes causing congenital heart diseases. Fast imaging technologies allow for the characterization of heartbeat parameters in the adult fly and there is growing evidence that cardiac dysfunction in human diseases could be reproduced and analyzed in Drosophila, as discussed here for heart defects associated with the myotonic dystrophy type 1. Overall, the power of genetics and unsuspected conservation of genes and pathways puts Drosophila at the heart of fundamental and applied cardiac research.

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Fetal echocardiography in Lithuania: traditions, significance and problems

Acta medica Lituanica ◽

10.15388/amed.2010.21684 ◽

2010 ◽

Vol 17 (3-4) ◽

pp. 116-122

Author(s):

Ramunė VANKEVIČIENĖ

Keyword(s):

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Diseases ◽

Fetal Echocardiography ◽

Heart Defects ◽

Tertiary Care ◽

Congenital Heart Diseases ◽

Conduction Disturbances ◽

Tertiary Care Centers ◽

Almost All

Background. The discovery of ultrasound has made a revolution in almost all fields of medicine. The past three decades have withessed an intensive development of fetal echocardiography methods and technique. The aim of the paper is to present a review of the results and trends of the last 10 years of fetal echocardiography in Lithuania and to show the spectrum and outcomes of prenatally detected congenital heart diseases. Materials and methods. Fetal echocardiography was performed for 1816 fetuses during the period from 1999 to 2009. Results. Cardiac pathology was diagnosed in 176 (9.7%) fetuses. Heart defects were detected in 112 (63.6%) of them, cardiac rhythm and conduction disturbances in 62 (35.2%), cardiomyopathy in 2 (1.1%) fetuses, and heart rhabdomyoma in 1 (0.6%) fetus. The general rate of the postnatal diagnosis of congenital heart defects in Lithuania was about 10%. Most of fetal cardiac diseases (70.5%) were diagnosed after 22 weeks of gestation. Because most of antenatally diagnosed congenital heart defects (74%) were critical and inconsistent with life, a large part of newborns (40.2%) died in the neonatal period, 10.7% of fetuses died in utero, and 8% of pregnancies were terminated by abortion. The data demonstrate good tendencies: the diagnosis has become earlier, a wider spectrum of diseases have been diagnosed, more newborns have survived. Our survey shows that 41.1% of newborns with prenatally diagnosed congenital heart defects have survived. Conclusions. 10% of severe congenital heart diseases are detected prenatally in Lithuania. The efficacy of antenatal diagnostics depends on the qualification of specialists, the number of tertiary care centers, on a successful collaboration among pediatric cardiologists, obstetricians and geneticists. The main problem is an insufficient preparation of obstetricians, the uncertified favor of pediatric cardiologist. Keywords: congenital heart disease, fetal echocardiography, antenatal diagnostics

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The Role of Telemedicine in Paediatric Cardiology

Telehealth Networks for Hospital Services ◽

10.4018/978-1-4666-2979-0.ch004 ◽

2013 ◽

pp. 44-88

Author(s):

Brian A. McCrossan ◽

Frank A. Casey

Keyword(s):

Economic Evaluation ◽

Medical Imaging ◽

Congenital Heart Defects ◽

Congenital Heart ◽

Heart Defects ◽

Pilot Project ◽

Clinical Service ◽

Current Evidence ◽

Paediatric Cardiology

Paediatric cardiology is a subspecialty ideally suited to telemedicine. A small number of experts cover large geographical areas and the diagnosis of congenital heart defects is largely dependent on the interpretation of medical imaging. Telemedicine has been applied to a number of areas within paediatric cardiology. However, its widespread uptake has been slow and fragmentary. In this chapter the authors examine the current evidence pertaining to telemedicine applied to paediatric cardiology, including their own experience, the importance of research and, in particular, economic evaluation in furthering telemedicine endeavours. Perhaps most importantly, they discuss the issues relating transitioning a pilot project into a sustainable clinical service.

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