Korean Circ J.  2015 Sep;45(5):357-361. 10.4070/kcj.2015.45.5.357.

Genetic Syndromes associated with Congenital Heart Disease

• Ko JM

• KMID: 2223797
• DOI: http://doi.org/10.4070/kcj.2015.45.5.357

Abstract

Recent research has demonstrated that genetic alterations or variations contribute considerably to the development of congenital heart disease. Many kinds of genetic tests are commercially available, and more are currently under development. Congenital heart disease is frequently accompanied by genetic syndromes showing both cardiac and extra-cardiac anomalies. Congenital heart disease is the leading cause of birth defects, and is an important cause of morbidity and mortality during infancy and childhood. This review introduces common genetic syndromes showing various types of congenital heart disease, including Down syndrome, Turner syndrome, 22q11 deletion syndrome, Williams syndrome, and Noonan syndrome. Although surgical techniques and perioperative care have improved substantially, patients with genetic syndromes may be at an increased risk of death or major complications associated with surgery. Therefore, risk management based on an accurate genetic diagnosis is necessary in order to effectively plan the surgical and medical management and follow-up for these patients. In addition, multidisciplinary approaches and care for the combined extra-cardiac anomalies may help to reduce mortality and morbidity accompanied with congenital heart disease.

Keyword

Heart defects, congenital; Down syndrome; Turner syndrome; 22q11 deletion syndrome; Williams syndrome; Noonan syndrome

MeSH Terms

22q11 Deletion Syndrome
Congenital Abnormalities
Diagnosis
Down Syndrome
Follow-Up Studies
Heart Defects, Congenital*
Humans
Mortality
Noonan Syndrome
Perioperative Care
Risk Management
Turner Syndrome
Williams Syndrome

Reference

1. Eskedal LT, Hagemo PS, Eskild A, Frøslie KF, Seiler S, Thaulow E. A population-based study relevant to seasonal variations in causes of death in children undergoing surgery for congenital cardiac malformations. Cardiol Young. 2007; 17:423–431.

2. Bray I, Wright DE, Davies C, Hook EB. Joint estimation of Down syndrome risk and ascertainment rates: a meta-analysis of nine published data sets. Prenat Diagn. 1998; 18:9–20.

3. Cleves MA, Hobbs CA, Cleves PA, Tilford JM, Bird TM, Robbins JM. Congenital defects among liveborn infants with Down syndrome. Birth Defects Res A Clin Mol Teratol. 2007; 79:657–663.

4. Bull MJ. Committee on Genetics. Health supervision for children with Down syndrome. Pediatrics. 2011; 128:393–406.

5. Marino B. Left-sided cardiac obstruction in patients with Down syndrome. J Pediatr. 1989; 115:834–835.

6. Carmi R, Boughman JA, Ferencz C. Endocardial cushion defect: further studies of "isolated" versus "syndromic" occurrence. Am J Med Genet. 1992; 43:569–575.

7. Tubman TR, Shields MD, Craig BG, Mulholland HC, Nevin NC. Congenital heart disease in Down's syndrome: two year prospective early screening study. BMJ. 1991; 302:1425–1427.

8. Tucker EM, Pyles LA, Bass JL, Moller JH. Permanent pacemaker for atrioventricular conduction block after operative repair of perimembranous ventricular septal defect. J Am Coll Cardiol. 2007; 50:1196–1200.

9. Stochholm K, Juul S, Juel K, Naeraa RW, Gravholt CH. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006; 91:3897–3902.

10. Prandstraller D, Mazzanti L, Picchio FM, et al. Turner's syndrome: cardiologic profile according to the different chromosomal patterns and long-term clinical follow-up of 136 nonpreselected patients. Pediatr Cardiol. 1999; 20:108–112.

11. Davenport ML. Approach to the patient with Turner syndrome. J Clin Endocrinol Metab. 2010; 95:1487–1495.

12. Bondy CA. Turner Syndrome Study Group. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007; 92:10–25.

13. Dulac Y, Pienkowski C, Abadir S, Tauber M, Acar P. Cardiovascular abnormalities in Turner's syndrome: what prevention? Arch Cardiovasc Dis. 2008; 101:485–490.

14. Botto LD, May K, Fernhoff PM, et al. A population-based study of the 22q11.2 deletion: phenotype, incidence, and contribution to major birth defects in the population. Pediatrics. 2003; 112:101–107.

15. McDonald-McGinn DM, Emanuel BS, Zackai EH. 22q11.2 Deletion syndrome. In : Pagon RA, Adam MP, Ardinger HH, editors. GeneReviews (R). Seattle (WA): University of Washington;1993.

16. Baldini A. Dissecting contiguous gene defects: TBX1. Curr Opin Genet Dev. 2005; 15:279–284.

17. Scambler PJ. The 22q11 deletion syndromes. Hum Mol Genet. 2000; 9:2421–2426.

18. Gerdes M, Solot C, Wang PP, et al. Cognitive and behavior profile of preschool children with chromosome 22q11.2 deletion. Am J Med Genet. 1999; 85:127–133.

19. Moss EM, Batshaw ML, Solot CB, et al. Psychoeducational profile of the 22q11.2 microdeletion: a complex pattern. J Pediatr. 1999; 134:193–198.

20. Oskarsdóttir S, Belfrage M, Sandstedt E, Viggedal G, Uvebrant P. Disabilities and cognition in children and adolescents with 22q11 deletion syndrome. Dev Med Child Neurol. 2005; 47:177–184.

21. Pierpont ME, Basson CT, Benson DW Jr, et al. Genetic basis for congenital heart defects: current knowledge: a scientific statement from the American Heart Association Congenital Cardiac Defects Committee, Council on Cardiovascular Disease in the Young: endorsed by the American Academy of Pediatrics. Circulation. 2007; 115:3015–3038.

22. Bassett AS, McDonald-McGinn DM, Devriendt K, et al. Practical guidelines for managing patients with 22q11.2 deletion syndrome. J Pediatr. 2011; 159:332–339.e1.

23. Committee on Genetics. American Academy of Pediatrics: health care supervision for children with Williams syndrome. Pediatrics. 2001; 107:1192–1204.

24. Strømme P, Bjørnstad PG, Ramstad K. Prevalence estimation of Williams syndrome. J Child Neurol. 2002; 17:269–271.

25. Adams GN, Schmaier AH. The Williams-Beuren Syndrome-a window into genetic variants leading to the development of cardiovascular disease. PLoS Genet. 2012; 8:e1002479.

26. Li DY, Toland AE, Boak BB, et al. Elastin point mutations cause an obstructive vascular disease, supravalvular aortic stenosis. Hum Mol Genet. 1997; 6:1021–1028.

27. Pober BR. Williams-Beuren syndrome. N Engl J Med. 2010; 362:239–252.

28. Kececioglu D, Kotthoff S, Vogt J. Williams-Beuren syndrome: a 30-year follow-up of natural and postoperative course. Eur Heart J. 1993; 14:1458–1464.

29. Zalzstein E, Moes CA, Musewe NN, Freedom RM. Spectrum of cardiovascular anomalies in Williams-Beuren syndrome. Pediatr Cardiol. 1991; 12:219–223.

30. Collins RT 2nd. Cardiovascular disease in Williams syndrome. Circulation. 2013; 127:2125–2134.

31. Collins RT 2nd, Kaplan P, Somes GW, Rome JJ. Long-term outcomes of patients with cardiovascular abnormalities and Williams syndrome. Am J Cardiol. 2010; 105:874–878.

32. van der Burgt I. Noonan syndrome. Orphanet J Rare Dis. 2007; 2:4.

33. Roberts AE, Allanson JE, Tartaglia M, Gelb BD. Noonan syndrome. Lancet. 2013; 381:333–342.

34. Ko JM, Kim JM, Kim GH, Yoo HW. PTPN11, SOS1, KRAS, and RAF1 gene analysis, and genotype-phenotype correlation in Korean patients with Noonan syndrome. J Hum Genet. 2008; 53:999–1006.

35. Lee BH, Kim JM, Jin HY, Kim GH, Choi JH, Yoo HW. Spectrum of mutations in Noonan syndrome and their correlation with phenotypes. J Pediatr. 2011; 159:1029–1035.

36. Aoki Y, Niihori T, Narumi Y, Kure S, Matsubara Y. The RAS/MAPK syndromes: novel roles of the RAS pathway in human genetic disorders. Hum Mutat. 2008; 29:992–1006.

37. Marino B, Digilio MC, Toscano A, Giannotti A, Dallapiccola B. Congenital heart diseases in children with Noonan syndrome: an expanded cardiac spectrum with high prevalence of atrioventricular canal. J Pediatr. 1999; 135:703–706.

38. Formigari R, Michielon G, Digilio MC, et al. Genetic syndromes and congenital heart defects: how is surgical management affected? Eur J Cardiothorac Surg. 2009; 35:606–614.

39. Shaw AC, Kalidas K, Crosby AH, Jeffery S, Patton MA. The natural history of Noonan syndrome: a long-term follow-up study. Arch Dis Child. 2007; 92:128–132.

40. Fahed AC, Gelb BD, Seidman JG, Seidman CE. Genetics of congenital heart disease: the glass half empty. Circ Res. 2013; 112:707–720.