Skip to main content
SpringerLink
Log in

Genetics of Congenital Heart Disease

  • Chapter
Fetal Cardiology

  • 1222 Accesses

Abstract

Congenital heart disease (CHD) is the most common congenital malformation accounting for one-third of all congenital abnormalities with an incidence of 7–10 per 1000 live births. Congenital heart disease may be associated with chromosomal aneuploidy and single gene disorders. However, an underlying chromosomal or genetic abnormality is found in less than 20% of patients with CHD. However, there is probably a genetic contribution to CHD even it has not been identified. The genetics of congenital heart disease is highly complex. Mutations in different genes can cause an identical malformation, whilst identical mutations in the same gene can result in a spectrum of cardiac malformations. Environmental factors play a major role in the development of cardiac malformations.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 79.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 129.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Benson DW, Martin LJ, Lo CW. Genetics of hypoplastic left heart syndrome. J Pediatr. 2016;173:25–31.

    Article  Google Scholar 

  • Brodwall K, Greve G, Leirgul E, Tell GS, Vollset SE, Øyen N. Recurrence of congenital heart defects among siblings—a nationwide study. Am J Med Genet. 2017;173(6):1575–85.

    Article  Google Scholar 

  • Burn J, Brennan P, Little J, Holloway S, Coffey R, Somerville J, Dennis NR, Allan L, Arnold R, Deanfield JE, Godman M, Houston A, Keeton B, Oakley C, Scott O, Silove E, Wilkinson J, Pembrey M, Hunter AS. Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet. 1998;351(9099):311–6.

    Article  CAS  Google Scholar 

  • Costain G, Silversides CK, Bassett AS. The importance of copy number variation in congenital heart disease. NPJ Genom Med. 2016;1:16031.

    Article  Google Scholar 

  • Digilio MC, Casey B, Toscano A, Calabrò R, Pacileo G, Marasini M, Banaudi E, Giannotti A, Dallapiccola B, Marino B. Complete transposition of the great arteries: patterns of congenital heart disease in familial precurrence. Circulation. 2001;104(23):2809–14.

    Article  CAS  Google Scholar 

  • Edwards JJ, Gelb BD. Genetics of congenital heart disease. Curr Opin Cardiol. 2016;31(3):235–41.

    Article  Google Scholar 

  • Emanuel BS, Budarf ML, Sellinger B, Goldmuntz E, Driscoll DA. Detection of microdeletions of 22q11.2 with fluorescence in situ hybridization (FISH): diagnosis of DiGeorge syndrome (DGS), velo-cardio-facial (VCF) syndrome, CHARGE association and conotruncal cardiac malformations. (Abstract). Am J Hum Genet. 1992;51(suppl):A3.

    Google Scholar 

  • Ferencz C, Rubin JD, Loffredo CA, Magee CA. Epidemiology of congenital heart disease: the Baltimore-Washington Infant Study, 1981–1989. New York: Futura Publishing Company; 1993.

    Google Scholar 

  • Ferreira C, Ziegler S, Gahl W. Generalized Arterial Calcification of Infancy. 2014. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews® [Internet]. Seattle, WA: University of Washington, Seattle; 1993–2017. https://www.ncbi.nlm.nih.gov/books/NBK253403/.

  • Freeze SL, Landis BJ, Ware SM, Helm BM. Bicuspid aortic valve: a review with recommendations for genetic counseling. J Genet Couns. 2016;25(6):1171–8.

    Article  Google Scholar 

  • Gelb BD, Chung WK. Complex genetics and the etiology of human congenital heart disease. Cold Spring Harb Perspect Med. 2014;4(7):a013953.

    Article  Google Scholar 

  • Hales AR, Mahle WT. Echocardiography screening of siblings of children with bicuspid aortic valve. Pediatrics. 2014;133(5):e1212–7.

    Article  Google Scholar 

  • Hinton RB Jr, Martin LJ, Tabangin ME, Mazwi ML, Cripe LH, Benson DW. Hypoplastic left heart syndrome is heritable. J Am Coll Cardiol. 2007;50:1590–5.

    Article  Google Scholar 

  • Isaacs H. Fetal and neonatal cardiac tumors. Pediatr Cardiol. 2004;25(3):252–73.

    Article  Google Scholar 

  • Kerstjens-Frederikse WS, van de Laar IM, Vos YJ, Verhagen JM, Berger RM, Lichtenbelt KD, Klein Wassink-Ruiter JS, van der Zwaag PA, du Marchie Sarvaas GJ, Bergman KA, Bilardo CM, Roos-Hesselink JW, Janssen JH, Frohn-Mulder IM, van Spaendonck-Zwarts KY, van Melle JP, Hofstra RM, Wessels MW. Cardiovascular malformations caused by NOTCH1 mutations do not keep left: data on 428 probands with left-sided CHD and their families. Genet Med. 2016;18(9):914–23.

    Article  CAS  Google Scholar 

  • Maslen CL. Molecular genetics of atrioventricular septal defects. Curr Opin Cardiol. 2004;19(3):205–10.

    Article  Google Scholar 

  • McBride KL, Pignatelli R, Lewin M, Ho T, Fernbach S, Menesses A, Lam W, Leal SM, Kaplan N, Schliekelman P, Towbin JA, Belmont JW. Inheritance analysis of congenital left ventricular outflow tract obstruction malformations: segregation, multiplex relative risk, and heritability. Am J Med Genet A. 2005;134A(2):180–6.

    Article  Google Scholar 

  • Moosmann J, Uebe S, Dittrich S, Rüffer A, Ekici AB, Toka O. Novel loci for non-syndromic coarctation of the aorta in sporadic and familial cases. PLoS One. 2015;10(5):e0126873.

    Article  Google Scholar 

  • Muntean I, Togănel R, Benedek T. Genetics of congenital heart disease: past and present. Biochem Genet. 2017;55(2):105–23.

    Article  CAS  Google Scholar 

  • Oliverio M, Digilio MC, Versacci P, Dallapiccola B, Marino B. Shells and heart: are human laterality and chirality of snails controlled by the same maternal genes? Am J Med Genet A. 2010;152A(10):2419–25.

    Article  Google Scholar 

  • Øyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK, Melbye M. Recurrence of congenital heart defects in families. Circulation. 2009;120(4):295–301.

    Article  Google Scholar 

  • Pedra SR, Smallhorn JF, Ryan G, Chitayat D, Taylor GP, Khan R, Abdolell M, Hornberger LK. Fetal cardiomyopathies: pathogenic mechanisms, hemodynamic findings, and clinical outcome. Circulation. 2002;106(5):585–91.

    Article  Google Scholar 

  • Barnes RM, Brian L, Black T. Nodal signaling and congenital heart defects. In: Nakanishi T, et al., editors. Etiology and morphogenesis of congenital heart disease. Tokyo, Japan: Springer; 2016.

    Google Scholar 

  • Rauch R, Hofbeck M, Zweier C, Koch A, Zink S, Trautmann U, Hoyer J, Kaulitz R, Singer H, Rauch A. Comprehensive genotype-phenotype analysis in 230 patients with tetralogy of Fallot. J Med Genet. 2010;47(5):321–31.

    Article  CAS  Google Scholar 

  • Seale AN, Uemura H, Webber SA, Partridge J, Roughton M, Ho SY, McCarthy KP, Jones S, Shaughnessy L, Sunnegardh J, Hanseus K, Berggren H, Johansson S, Rigby ML, Keeton BR, Daubeney PE, British Congenital Cardiac Association. Total anomalous pulmonary venous connection: morphology and outcome from an international population-based study. Circulation. 2010;122(25):2718–26.

    Article  Google Scholar 

  • Seale AN, Carvalho JS, Gardiner HM, Mellander M, Roughton M, Simpson J, Tometzki A, Uzun O, Webber SA, Daubeney PE, British Congenital Cardiac Association. Total anomalous pulmonary venous connection: impact of prenatal diagnosis. Ultrasound Obstet Gynecol. 2012;40(3):310–8.

    Article  CAS  Google Scholar 

  • Sivasankaran S, Sharland GK, Simpson JM. Dilated cardiomyopathy presenting during fetal life. Cardiol Young. 2005;15(4):409–16.

    Article  Google Scholar 

  • Soemedi R, Wilson IJ, Bentham J, Darlay R, Töpf A, Zelenika D, Cosgrove C, Setchfield K, Thornborough C, Granados-Riveron J, Blue GM, Breckpot J, Hellens S, Zwolinkski S, Glen E, Mamasoula C, Rahman TJ, Hall D, Rauch A, Devriendt K, Gewillig M, O’Sullivan J, Winlaw DS, Bu'Lock F, Brook JD, Bhattacharya S, Lathrop M, Santibanez-Koref M, Cordell HJ, Goodship JA, Keavney BD. Contribution of global rare copy-number variants to the risk of sporadic congenital heart disease. Am J Hum Genet. 2012;91(3):489–501.

    Article  CAS  Google Scholar 

  • Su W, Zhu P, Wang R, Wu Q, Wang M, Zhang X, Mei L, Tang J, Kumar M, Wang X, Su L, Dong N. Congenital heart diseases and their association with the variant distribution features on susceptibility genes. Clin Genet. 2017;91(3):349–54.

    Article  CAS  Google Scholar 

  • Sutherland MJ, Ware SM. Disorders of left-right asymmetry: heterotaxy and situs inversus. Am J Med Genet C Semin Med Genet. 2009;151C(4):307–17.

    Article  CAS  Google Scholar 

  • Unolt M, Putotto C, Silvestri LM, Marino D, Scarabotti A, Massaccesi V, Caiaro A, Versacci P, Marino B. Transposition of great arteries: new insights into the pathogenesis. Front Pediatr. 2013;1:11.

    Article  Google Scholar 

  • Wacker-Gussmann A, Strasburger JF, Cuneo BF, Wakai RT. Diagnosis and treatment of fetal arrhythmia. Am J Perinatol. 2014;31(7):617–28.

    Article  Google Scholar 

  • Wapner RJ, Martin CL, Levy B, Ballif BC, Eng CM, Zachary JM, Savage M, Platt LD, Saltzman D, Grobman WA, Klugman S, Scholl T, Simpson JL, McCall K, Aggarwal VS, Bunke B, Nahum O, Patel A, Lamb AN, Thom EA, Beaudet AL, Ledbetter DH, Shaffer LG, Jackson L. Chromosomal microarray versus karyotyping for prenatal diagnosis. N Engl J Med. 2012;367(23):2175–84.

    Article  CAS  Google Scholar 

  • Weber R, Kantor P, Chitayat D, Friedberg MK, Golding F, Mertens L, Nield LE, Ryan G, Seed M, Yoo SJ, Manlhiot C, Jaeggi E. Spectrum and outcome of primary cardiomyopathies diagnosed during fetal life. JACC Heart Fail. 2014;2(4):403–11.

    Article  Google Scholar 

  • Zaidi S, Brueckner M. Genetics and genomics of congenital heart disease. Circ Res. 2017;120(6):923–40.

    Article  CAS  Google Scholar 

  • Zhang Y, Ai F, Zheng J, Peng B. Associations of GATA4 genetic mutations with the risk of congenital heart disease: A meta-analysis. Medicine (Baltimore). 2017;96(18):e6857.

    Article  CAS  Google Scholar 

Useful Websites

Download references

Author information

Authors and Affiliations

  1. St George’s University Hospitals NHS Foundation Trust, London, UK

    Sahar Mansour

Authors
  1. Sahar Mansour
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sahar Mansour .

Editor information

Editors and Affiliations

  1. Evelina London Children’s Hospital, Guy’s and St Thomas’ NHS Foundation Trust, London, UK

    John Simpson , Vita Zidere  & Owen I. Miller ,  & 

  2. King’s College Hospital, NHS Foundation Trust, London, UK

    Vita Zidere

Electronic Supplementary Material

Four chamber view of a fetus with non-compaction of the myocardium. The apices of both left and right ventricles are abnormally trabeculated with deep recesses (crypts) (MP4 3741 kb)

Four chamber view of a fetus with non-compaction of the myocardium with the addition of colour flow Doppler to demonstrate the deep crypts within the myocardium of the left and right ventricles which are pathognomonic of this condition (MP4 2758 kb)

This video shows a large cystic teratoma in association with fetal hydrops (WMV 612 kb)

This fetus has a large teratoma with typical non-uniform echogenicity. It may be impossible to visualise the point of attachment of the teratoma to the heart or outflow tracts. Most are attached to the aorta (WMV 941 kb)

This video shows the echogenicity of both the descending aorta and of the right pulmonary artery (AVI 34606 kb)

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Cite this chapter

Mansour, S. (2018). Genetics of Congenital Heart Disease. In: Simpson, J., Zidere, V., Miller, O.I. (eds) Fetal Cardiology. Springer, Cham. https://doi.org/10.1007/978-3-319-77461-9_15

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-77461-9_15

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-77460-2

  • Online ISBN: 978-3-319-77461-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation