The genetics of congenital heart disease

2018 ◽  
Author(s):  
James R. Bentham
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Rare Variants ◽  
Copy Number Variants ◽  
Recurrence Risk ◽  
Model Organisms ◽  
Future Challenges ◽  
New Research ◽  
Made In

Congenital heart disease (CHD) is defined as a structural cardiac malformation resulting from an abnormality of development; 8% of CHD is inherited in a Mendelian fashion and 12% results from chromosomal imbalance. Recurrence risk and new research suggest that even the remaining 80% of patients without an identifiable familial or syndromic basis for disease may have an identifiable genetic cause. The potential to understand these mechanisms is increasing with the advent of new sequencing techniques which have identified multiple or single rare variants and/or copy number variants clustering in cardiac developmental genes as well as common variants that may also contribute to disease, for example by altering metabolic pathways. Work in model organisms such as mouse and zebrafish has been pivotal in identifying CHD candidate genes. Future challenges involve translating the discoveries made in mouse models to human CHD genetics and manipulating potentially protective pathways to prevent disease.

scholarly journals Genetic Etiology of Left‐Sided Obstructive Heart Lesions: A Story in Development

2021 ◽  
Vol 10 (2) ◽  
Author(s):  
Lauren E. Parker ◽  
Andrew P. Landstrom
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
Rare Variants ◽  
Cardiac Development ◽  
Coarctation Of The Aorta ◽  
Recurrence Risk ◽  
Interrupted Aortic Arch ◽  
Genetic Associations ◽  
Genetic Sequencing

Abstract Congenital heart disease is the most common congenital defect observed in newborns. Within the spectrum of congenital heart disease are left‐sided obstructive lesions (LSOLs), which include hypoplastic left heart syndrome, aortic stenosis, bicuspid aortic valve, coarctation of the aorta, and interrupted aortic arch. These defects can arise in isolation or as a component of a defined syndrome; however, nonsyndromic defects are often observed in multiple family members and associated with high sibling recurrence risk. This clear evidence for a heritable basis has driven a lengthy search for disease‐causing variants that has uncovered both rare and common variants in genes that, when perturbed in cardiac development, can result in LSOLs. Despite advancements in genetic sequencing platforms and broadening use of exome sequencing, the currently accepted LSOL‐associated genes explain only 10% to 20% of patients. Further, the combinatorial effects of common and rare variants as a cause of LSOLs are emerging. In this review, we highlight the genes and variants associated with the different LSOLs and discuss the strengths and weaknesses of the present genetic associations. Furthermore, we discuss the research avenues needed to bridge the gaps in our current understanding of the genetic basis of nonsyndromic congenital heart disease.

scholarly journals Familial congenital heart disease in Bandung, Indonesia

2013 ◽  
Vol 53 (3) ◽  
pp. 173
Author(s):  
Sri Endah Rahayuningsih
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Dilated Cardiomyopathy ◽  
Congenital Heart ◽  
Family Studies ◽  
Recurrence Risk ◽  
Descriptive Study ◽  
Pedigree Analysis ◽  
Tricuspid Atresia ◽  
History Of

Background Congenital heart disease (CHD) may occur inseveral members of a family. Studies have shown that familialgenetic factor play a role in CHD.Objective To identify familial recurrences of CHD in familieswith at least one member treated for CHD in Dr. Hasan SadikinHospital, Bandung Indonesia.Methods In this descriptive study, subjects were CHD patientshospitalized or treated from January 2005 to December 2011. Weconstructed family pedigrees for five families.Results During the study period, there were 1,779 patients withCHD. We found 5 families with 12 familial CHD cases, consistingof 8 boys and 4 girls. Defects observed in these 12 patients weretetralogy of Fallot, transposition of the great arteries, persistentductus arteriosus, ventricular septa! defect, tricuspid atresia,pulmonary stenos is, and dilated cardiomyopathy. Persistent ductusarteriosus was the most frequently observed defect (4 out of 12subjects) . None of the families had a history of consanguinity. Therecurrence risk of CHD among siblings was calculated to be 0.67%,and the recurrence risk ofCHD among cousins was 0.16%.Conclusion Familial CHD may indicate the need for geneticcounseling and further pedigree analysis.

Conotruncal Malformation Complex: Examples of Possible Monogenic Inheritance

PEDIATRICS ◽  
1979 ◽  
Vol 63 (6) ◽  
pp. 890-893
Author(s):  
Marvin E. Miller ◽  
David W. Smith
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Family History ◽  
Congenital Heart ◽  
Recurrence Risk ◽  
Strong Family History ◽  
Cardiac Defects ◽  
Monogenic Inheritance ◽  
Congenital Cardiac Defects ◽  
Malformation Complex

Two families are described in which there is possible monogenic inheritance of congenital cardiac defects within the spectrum of faulty conotruncal septation (CTS). Evidence for a genetic control of conotruncal septation arises from genetic and embryologic studies of similar defects in the Keeshond dog model, the excess of sibship pairs with conotruncal septation defects in sibship pairs with congenital heart disease, and previously reported pedigrees of families with multiple affected individuals with conotruncal septation defects. It is suggested that in the small number of cases of congenital cardiac defects in which there is a strong family history for CTS defects, a higher recurrence risk should be considered rather than the usual polygenic recurrence risk of 3% that is usually given in such situations.

scholarly journals Rare variants in SOX17 are associated with pulmonary arterial hypertension with congenital heart disease

2018 ◽  
Vol 10 (1) ◽  
Author(s):  
Na Zhu ◽  
Carrie L. Welch ◽  
Jiayao Wang ◽  
Philip M. Allen ◽  
Claudia Gonzaga-Jauregui ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Rare Variants ◽  
Pulmonary Arterial

scholarly journals Preconceptual Folic Acid Use and Recurrence Risk Counseling for Congenital Heart Disease

2014 ◽  
Vol 10 (3) ◽  
pp. 219-225 ◽  
Author(s):  
Shabnam Peyvandi ◽  
Jack Rychik ◽  
Xuemei Zhang ◽  
Judy A. Shea ◽  
Elizabeth Goldmuntz
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Folic Acid ◽  
Congenital Heart ◽  
Recurrence Risk

scholarly journals Contribution of Global Rare Copy-Number Variants to the Risk of Sporadic Congenital Heart Disease

2012 ◽  
Vol 91 (3) ◽  
pp. 489-501 ◽  
Author(s):  
Rachel Soemedi ◽  
Ian J. Wilson ◽  
Jamie Bentham ◽  
Rebecca Darlay ◽  
Ana Töpf ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Copy Number ◽  
Congenital Heart ◽  
Copy Number Variants

scholarly journals Copy Number Variants and Exome Sequencing Analysis in Six Pairs of Chinese Monozygotic Twins Discordant for Congenital Heart Disease

2017 ◽  
Vol 20 (6) ◽  
pp. 521-532 ◽  
Author(s):  
Yuejuan Xu ◽  
Tingting Li ◽  
Tian Pu ◽  
Ruixue Cao ◽  
Fei Long ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Exome Sequencing ◽  
Copy Number ◽  
Congenital Heart ◽  
Copy Number Variants ◽  
Genetic Mutation ◽  
Sequencing Analysis ◽  
Susceptibility Loci ◽  
Mz Twins

Congenital heart disease (CHD) is one of the most common birth defects. More than 200 susceptibility loci have been identified for CHDs, yet a large part of the genetic risk factors remain unexplained. Monozygotic (MZ) twins are thought to be completely genetically identical; however, discordant phenotypes have been found in MZ twins. Recent studies have demonstrated genetic differences between MZ twins. We aimed to test whether copy number variants (CNVs) and/or genetic mutation differences play a role in the etiology of CHDs by using single nucleotide polymorphism (SNP) genotyping arrays and whole exome sequencing of twin pairs discordant for CHDs. Our goal was to identify mutations present only in the affected twins, which could identify novel candidates for CHD susceptibility loci. We present a comprehensive analysis for the CNVs and genetic mutation results of the selected individuals but detected no consistent differences within the twin pairs. Our study confirms that chromosomal structure or genetic mutation differences do not seem to play a role in the MZ twins discordant for CHD.

scholarly journals FISH spots microdeletion in heart defects

2009 ◽  
Vol 15 (S3) ◽  
pp. 5-6
Author(s):  
P. Ferraz-Gameiro ◽  
J. Ferrão ◽  
C. Mendes ◽  
L. M. Pires ◽  
E. Matoso ◽  
...  
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Congenital Heart ◽  
De Novo ◽  
Heart Defects ◽  
Autosomal Dominant Trait ◽  
Conotruncal Malformations ◽  
Wide Range ◽  
22Q11.2 Microdeletion ◽  
Made In

AbstractThe 22q11.2 microdeletion is found in most of DiGeorge and velocardiofacial syndromes. These individuals have a wide range of anomalies including congenital heart disease, palatal abnormalities, characteristic facial features, hypocalcaemia, immune deficiency, and learning difficulties. Congenital heart disease, particularly conotruncal malformations are associated with 29% of deletions. This syndrome may be inherited as an autosomal dominant trait, but the majority of patients (93%) have a de novo deletion. To access the presence of the microdeletion in those individuals whose phenotipic changes suggested abnormalities in chromosome 22, a study has been made in several children with congenital heart defects.

scholarly journals Evaluation and Management of Pulmonary Arterial Hypertension in Congenital Heart Disease

2021 ◽  
Vol 17 (2) ◽  
pp. 145-151
Author(s):  
Hassaan Arshad ◽  
Valeria Duarte
Keyword(s):  
Congenital Heart Disease ◽  
Heart Disease ◽  
Pulmonary Arterial Hypertension ◽  
Arterial Hypertension ◽  
Congenital Heart ◽  
Cardiac Defect ◽  
Targeting Therapy ◽  
Pulmonary Vasodilators ◽  
Pulmonary Arterial ◽  
Made In

Pulmonary arterial hypertension is a common complication in patients with congenital heart disease (CHD), aggravating the natural course of the underlying defect. Pulmonary arterial hypertension (PAH) has a multifactorial etiology depending on the size and nature of the cardiac defect as well as environmental factors. Although progress has been made in disease-targeting therapy using pulmonary vasodilators to treat Eisenmenger syndrome, important gaps still exist in the evaluation and management of adult patients with CHD-associated PAH (PAH-CHD) who have systemic-to-pulmonary shunts. The choice of interventional, medical, or both types of therapy is an ongoing dilemma that requires further data. This review focuses on the evaluation and management of PAH-CHD in the contemporary era.

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