Hostname: page-component-586b7cd67f-t7fkt Total loading time: 0 Render date: 2024-11-22T13:37:55.485Z Has data issue: false hasContentIssue false
  • English
  • Français

Congenital cardiac disease and inbreeding: specific defects escape higher risk due to parental consanguinity

Published online by Cambridge University Press:  27 June 2007

Ghassan Chehab ,
Philippe Chedid ,
Zakhia Saliba  and
Patrice Bouvagnet
Ghassan Chehab
Affiliation:
Department of Paediatrics, Lebanese University, Faculty of Medical Sciences, Hadath, Greater Beirut, Lebanon Paediatric Department, CHU Hôtel-Dieu de France, Beirut, Lebanon
Philippe Chedid
Affiliation:
Department of Paediatrics, Lebanese University, Faculty of Medical Sciences, Hadath, Greater Beirut, Lebanon
Zakhia Saliba
Affiliation:
Paediatric Department, CHU Hôtel-Dieu de France, Beirut, Lebanon
Patrice Bouvagnet*
Affiliation:
Laboratoire Cardiogénétique, ERM 0107INSERM, Bron, France Service de Cardiologie Pédiatrique, Groupe Hospitalier Est, Hospices Civils de Lyon, Bron, France Université Lyon 1, Lyon, France
*
Correspondence to: Patrice Bouvagnet, MD, PhD, Laboratoire de Cardiogénétique, Groupe Hospitalier Est, 28 Avenue Doyen Lépine, 69677 Bron cedex, France. Tel: +33 472 12 96 76; Fax: +33 472 35 70 49; E-mail: [email protected]
Get access Rights & Permissions [Opens in a new window]

Abstract

Aims

To test on a large cohort whether parental consanguinity varies among different types of congenitally malformed hearts.

Methods and Results

Between 1 May, 1999, and 28 February, 2006, a large cohort of 1585 newly diagnosed cases with non-syndromic congenitally malformed heart was enrolled at the National Register of Paediatric and Congenital Heart Disease, Lebanese Society of Cardiology, Beirut. Another group, made up of 1979 cases referred to the National Register of Paediatric and Congenital Heart Disease, but free of any malformation, and with a rate of consanguinity similar to a recent survey made by UNICEF in Lebanon, was used for the purposes of control. We used the Chi-squared test, and ratio of risk, to compare the groups.

Subgroups with first degree cousins, first plus second degree cousins, and any degree of consanguinity, are significantly larger in the cohort with congenitally malformed hearts than in the control cohort, with proportions of 19.4%, 25.7%, and 27.4% versus 14.4%, 20.3%, and 23.9%, respectively. Those with tetralogy of Fallot, valvar aortic stenosis, and atrial septal defect have a significantly higher percentage of consanguineous parents than do the controls. By contrast, this is not the case for those with atrioventricular septal defect and common atrioventricular junction (“atrioventricular canal”), or discordant ventriculo-arterial connections (“transposition”). These differences persist when the types of congenital cardiac defect types are pooled according to presumed embryological processes. Those with hypoplasia of the left heart have increased parental consanguinity, but not the group of various types of discordant ventriculo-arterial connections.

Conclusion

Only some types of congenitally malformed hearts have an increased percentage of parental consanguinity, suggesting that those types with no increased risk due to parental consanguinity are determined by genetic factors that are X-linked or exclusively autosomal dominant.

Keywords

ConsanguinityLebanoncongenital heart disease
Type
Original Article
Information
Cardiology in the Young , Volume 17 , Issue 4 , August 2007 , pp. 414 - 422
Copyright
Copyright © Cambridge University Press 2007

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

Footnotes

*

Sources of financial support: Research work of Dr. P. Bouvagnet and Laboratoire de CardioGénétique is supported by Foundation Renaud FEBVRE and the Programme Franco-Libanais Cèdre.

References

1. Petrini, J, Damus, K, Russell, R, Poschman, K, Davidoff, MJ, Mattison, D. Contribution of birth defects in infant mortality in the United States. Teratology 2002; 66 (Suppl 1): S3–6.CrossRefGoogle ScholarPubMed
2. Whittemore, R, Wells, JA, Castellsague, X. A second-generation study of 427 probands with congenital heart defects and their 837 children. J Am Coll Cardiol 1994; 23: 1459–1467.CrossRefGoogle ScholarPubMed
3. Burn, J, Brennan, P, Little, J, et al. . Recurrence risks in offspring of adults with major heart defects: results from first cohort of British collaborative study. Lancet 1998; 351: 311–316.CrossRefGoogle ScholarPubMed
4. Gatrad, AR, Read, AP, Watson, GH. Consanguinity and complex cardiac anomalies with situs ambiguus. Arch Dis Child 1984; 59: 242–245.CrossRefGoogle ScholarPubMed
5. Gev, D, Roguin, N, Freundlich, E. Consanguinity and congenital heart disease in the rural Arab population in northern Israel. Hum Hered 1986; 36: 213–217.CrossRefGoogle ScholarPubMed
6. Badaruddoza, , Afzal, M, Akhtaruzzaman, . Inbreeding and congenital heart diseases in a North Indian population. Clin Genet 1994; 45: 288–291.CrossRefGoogle Scholar
7. Becker, SM, Al-Halees, Z. First-cousin matings and congenital heart disease in Saudi Arabia. Community Genet 1999; 2: 69–73.Google ScholarPubMed
8. Bassili, A, Mokhtar, SA, Dabous, NI, Zaher, SR, Mokhtar, MM, Zaki, A. Risk factors for congenital heart diseases in Alexandria, Egypt. Eur J Epidemiol 2000; 6: 805–814.CrossRefGoogle Scholar
9. Nabulsi, MM, Tamim, H, Sabbagh, M, Obeid, MY, Yunis, KA, Bitar, FF. Parental consanguinity and congenital heart malformations in a developing country. Am J Med Genet 2003; 116A: 342–347.CrossRefGoogle ScholarPubMed
10. Subramanyan, R, Joy, J, Venugopalan, P, Al Khusaiby, S. Incidence and spectrum of congenital heart disease in Oman. Ann Trop Paediatr 2000; 20: 337–341.CrossRefGoogle ScholarPubMed
11. Robida, A, Folger, GM, Hajar, HA. Incidence of congenital heart disease in Qatari children. Int J Cardiol 1997; 60: 19–22.CrossRefGoogle ScholarPubMed
12. Becker, SM, Al-Halees, Z, Molina, C, Paterson, RM. Consanguinity and congenital heart disease in Saudi Arabia. Am J Med Genet 2001; 99: 3–13.3.0.CO;2-U>CrossRefGoogle ScholarPubMed
13. Pradat, P, Francannet, C, Harris, JA, Robert, E. The epidemiology of cardiovascular defects, Part I: A study based on data from three large registries of congenital malformations. Pediatr Cardiol 2003; 24: 195–221.CrossRefGoogle Scholar
14. U.N.I.C.E.F. Condition of children in Lebanon 2000. U.N.I.C.E.F. and the Central Agency for Statistics, 2000, 31–33.Google Scholar
15. Stoltenberg, C, Magnus, P, Lie, RT, Daltveit, AK, Irgens, LM. Birth defects and parental consanguinity in Norway. Am J Epidemiol 1997; 145: 439–448.CrossRefGoogle ScholarPubMed
16. World Health Organization. Community control of genetics and congenital disorders. In: EMRO technical publications, series 24. Eastern Mediterranean Regional Office. Alexandria. 1997: 79.Google Scholar
17. Schott, JJ, Benson, DW, Basson, CT, et al. . Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science 1998; 281: 108–111.CrossRefGoogle ScholarPubMed
18. Garg, V, Kathiriya, IS, Barnes, R, et al. . GATA4 mutations cause human congenital heart defects and reveal an interarction with TBX5. Nature 2003; 424: 443–447.CrossRefGoogle ScholarPubMed
19. Ching, YH, Ghosh, TK, Cross, SJ, et al. . Mutation in myosin heavy chain 6 causes atrial septal defect. Nat Genet 2005; 37: 423–428.CrossRefGoogle ScholarPubMed
20. Garg, V, Muth, AN, Ransom, JF, et al. . Mutations in NOTCH1 cause aortic valve disease. Nature 2005; 437: 270–274.CrossRefGoogle ScholarPubMed
21. Digilio, MC, Marino, B, Giannotti, A, Toscano, A, Dallapiccola, B. Recurrence risk figures for isolated tetralogy of Fallot after screening for 22q11 microdeletion. J Med Genet 1997; 34: 188–190.CrossRefGoogle ScholarPubMed
22. Wulfsberg, EA, Zintz, EJ, Moore, JW. The inheritance of conotruncal malformations: a review and report of two siblings with tetralogy of Fallot with pulmonary atresia. Clin Genet 1991; 40: 12–16.CrossRefGoogle ScholarPubMed
23. Goldmuntz, E, Geiger, E, Benson, W. NKX2.5 mutations in patients with tetralogy of Fallot. Circulation 2001; 104: 2565–2568.CrossRefGoogle ScholarPubMed
24. Pizzuti, A, Sarkozy, A, Newton, AL, et al. . Mutations of ZFPM2/FOG2 gene in sporadic cases of tetralogy of Fallot. Hum Mutat 2003; 22: 372–377.CrossRefGoogle ScholarPubMed
25. Nemer, G, Fadlalah, F, Usta, J, et al. . A novel mutation in the GATA4 gene in patients with tetralogy of Fallot. Hum Mutat 2006; 27: 293–294Mutation in Brief #881 Online.CrossRefGoogle ScholarPubMed
26. O’Nuallain, S, Hall, JG, Stamm, SJ. Autosomal dominant inheritance of endocardial cushion defect. Birth Defects Orig Artic Ser 1977; 13: 143–147.Google ScholarPubMed
27. Wilson, L, Curtis, A, Korenberg, JR, et al. . A large, dominant pedigree of atrioventricular septal defect (AVSD): exclusion from the Down syndrome critical region on chromosome 21. Am J Hum Genet 1993; 53: 1262–1268.Google ScholarPubMed
28. Digilio, MC, Marino, B, Cicini, MP, Giannotti, A, Formigari, R, Dallapiccola, B. Risk of congenital heart defects in relatives of patients with atrioventricular canal. Am J Dis Child 1993; 147: 1295–1297.Google ScholarPubMed
29. Kumar, A, Williams, CA, Victoria, BE. Familial atrioventricular septal defect: possible genetic mechanisms. Br Heart J 1994; 71: 79–81.CrossRefGoogle ScholarPubMed
30. Sheffield, VC, Pierpont, ME, Nishimura, D, et al. . Identification of a complex congenital heart defect susceptibility locus by using DNA pooling and shared segment analysis. Hum Mol Genet 1997; 6: 117–121.CrossRefGoogle ScholarPubMed
31. Robinson, SW, Morris, CD, Goldmuntz, E, et al. . Missense mutations in CRELD1 are associated with cardiac atrioventricular septal defects. Am J Hum Genet 2003; 72: 1047–1052.CrossRefGoogle ScholarPubMed
32. Zatyka, M, Priestley, M, Ladusans, EJ, et al. . Analysis of CRELD1 as a candidate 3p25 atrioventricular septal defect locus (AVSD2). Clin Genet 2005; 67: 526–528.CrossRefGoogle Scholar
33. Bamford, RN, Roessler, R, Burdine, RD, et al. . Loss-of-function mutations in the EGF-CFC gene CFC1 are associate with human left-right laterality defects. Nat Genet 2000; 26: 365–369.CrossRefGoogle ScholarPubMed
34. Megarbane, A, Salem, N, Stephan, E, et al. . X-linked transposition of the great arteries and incomplete penetrance among males with a nonsense mutation in ZIC3. Eur J Hum Genet 2000; 8: 704–708.CrossRefGoogle ScholarPubMed
35. Digilio, MC, Casey, B, Toscano, A, et al. . Complete transposition of the great arteries: patterns of congenital heart disease in familial precurrence. Circulation 2001; 104: 2809–2814.CrossRefGoogle ScholarPubMed
36. Piacentini, G, Digilio, MC, Capolino, R, et al. . Familial recurrence of heart defects i subjects with congenitally corrected transposition of the great arteries. Am J Med Genet 2005; 137A: 176–180.CrossRefGoogle Scholar