Influence of genes and the environment in familial congenital heart defects

Wang,Xike; Li,Pingjuan; Chen,Sun; Xi,Lili; Guo,Ying; Guo,Aihua; Sun,Kun

doi:10.3892/mmr.2013.1847

Influence of genes and the environment in familial congenital heart defects

Authors:
- Xike Wang
- Pingjuan Li
- Sun Chen
- Lili Xi
- Ying Guo
- Aihua Guo
- Kun Sun
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Affiliations: Children's Heart Center, Xinhua Hospital Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200092, P.R. China, Department of Cardiology, Shanghai Children's Medical Center Affiliated with Shanghai Jiao Tong University School of Medicine, Shanghai 200127, P.R. China
Published online on: December 6, 2013 https://doi.org/10.3892/mmr.2013.1847
Pages: 695-700

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Abstract

The present study aimed to investigate genetic and environmental factors involved in the pathogenesis of congenital heart disease (CHD). A total of 61 familial pedigrees with CHD were analyzed, and 134 patients out of 761 family members had a diagnosis of CHD confirmed. The present study revealed that the prevalence of CHD in first‑degree relatives (55/249, 22.0%) was significantly higher than that in second‑degree relatives (18/526, 3.4%). Additionally, the recurrence rate of CHD in families in which the patient's mother (12/61) or sister (15/61) had CHD were significantly higher than in cases with the father (6/61) or brother (4/61) having CHD. The subtypes of CHD with increased risk of recurrence were ventricle septal defect (VSD) and atrial septal defect (ASD), followed by patent ductus arteriosus and tetralogy of fallot (TOF). In the 21 sets of twins among the 61 familial pedigrees analyzed, the concordance of both twins affected by CHD in identical and dizygotic twins was 94.4% (17/18) and 33.3% (1/3), respectively. Identical subtypes of CHD were identified in 10 out of 21 sets of twins. Of note, the following pattern was identified in three sets of the twins: One twin had TOF, while the other one had VSD. A risk factor survey revealed that threatened abortion in early pregnancy was associated with familial CHD. In conclusion, genetic factors may have important roles in the development of CHD, and TOF and VSD may have similar molecular mechanisms. Threatened abortion in early pregnancy is a novel environmental factor that may be specific in Chinese females with CHD.

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1	Hoffman JI and Kaplan S: The incidence of congenital heart disease. J Am Coll Cardiol. 39:1890–1900. 2002. View Article : Google Scholar
2	van der Linde D, Konings EE, Slager MA, Witsenburg M, Helbing WA, Takkenberg JJ and Roos-Hesselink JW: Birth prevalence of congenital heart disease worldwide: a systematic review and meta-analysis. J Am Coll Cardiol. 58:2241–2247. 2011.PubMed/NCBI
3	Fesslova V, Brankovic J, Lalatta F, Villa L, Meli V, Piazza L and Ricci C: Recurrence of congenital heart disease in cases with familial risk screened prenatally by echocardiography. J Pregnancy. 2011:3680672011. View Article : Google Scholar : PubMed/NCBI
4	Nora JJ: Multifactorial inheritance hypothesis for the etiology of congenital heart disease: the genetic-environmental interaction. Circulation. 38:604–617. 1968. View Article : Google Scholar
5	Basson CT, Bachinsky DR, Lin RC, et al: Mutations in human TBX5 [corrected] cause limb and cardiac malformation in Holt-Oram syndrome. Nat Genet. 15:30–35. 1997.
6	Schott JJ, Benson DW, Basson CT, Pease W, Silberbach GM, Moak JP, Maron BJ, Seidman CE and Seidman JG: Congenital heart disease caused by mutations in the transcription factor NKX2-5. Science. 281:108–111. 1998. View Article : Google Scholar : PubMed/NCBI
7	Garg V, Kathiriya IS, Barnes R, et al: GATA4 mutations cause congenital heart defects and reveal an interaction with TBX5. Nature. 424:443–447. 2003. View Article : Google Scholar : PubMed/NCBI
8	Butler TL, Esposito G, Blue GM, et al: GATA4 mutations in 357 unrelated patients with congenital heart malformation. Genet Test Mol Biomarkers. 14:797–802. 2010. View Article : Google Scholar : PubMed/NCBI
9	Brent RL: Environmental causes of human congenital malformations: the pediatrician’s role in dealing with these complex clinical problems caused by a multiplicity of environmental and genetic factors. Pediatrics. 113(4 Suppl): 957–968. 2004.
10	Polifka JE and Friedman JM: Medical genetics: 1. Clinical teratology in the age of genomics. CMAJ. 167:265–273. 2002.PubMed/NCBI
11	Autti-Rämö I, Fagerlund A, Ervalahti N, Loimu L, Korkman M and Hoyme HE: Fetal alcohol spectrum disorders in Finland: clinical delineation of 77 older children and adolescents. Am J Med Genet A. 140:137–143. 2006.PubMed/NCBI
12	Ferencz C, Loffredo CA, Correa-Villasenor A and Wilson PD: Genetic and Environmental Risk Factors of Major Congenital Heart Disease: The Baltimore-Washington Infant Study 1981–1989. 5. Futura Publishing Company; Armonk, NY: 1997
13	Wren C, Birrell G and Hawthorne G: Cardiovascular malformations in infants of diabetic mothers. Heart. 89:1217–1220. 2003. View Article : Google Scholar : PubMed/NCBI
14	Botto LD, Olney RS and Erickson JD: Vitamin supplements and the risk for congenital anomalies other than neural tube defects. Am J Med Genet C Semin Med Genet. 125C:12–21. 2004. View Article : Google Scholar : PubMed/NCBI
15	Wolf M and Basson CT: The molecular genetics of congenital heart disease: a review of recent developments. Curr Opin Cardiol. 25:192–197. 2010. View Article : Google Scholar : PubMed/NCBI
16	Wang X, Wang J, Zhao P, Guo Y, Wu L, Sun J and Sun K: Familial congenital heart disease: data collection and preliminary analysis. Cardiol Young. 23:394–399. 2013. View Article : Google Scholar : PubMed/NCBI
17	Hoess K, Goldmuntz E and Pyeritz RE: Genetic counseling for congenital heart disease: new approaches for a new decade. Curr Cardiol Rep. 4:68–75. 2002. View Article : Google Scholar : PubMed/NCBI
18	Bruneau BG: The developmental genetics of congenital heart disease. Nature. 451:943–948. 2008. View Article : Google Scholar : PubMed/NCBI
19	Øyen N, Poulsen G, Boyd HA, Wohlfahrt J, Jensen PK and Melbye M: Recurrence of congenital heart defects in families. Circulation. 120:295–301. 2009.
20	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. 351:311–316. 1998. View Article : Google Scholar : PubMed/NCBI
21	Calcagni G, Digilio MC, Sarkozy A, Dallapiccola B and Marino B: Familial recurrence of congenital heart disease: an overview and review of the literature. Eur J Pediatr. 166:111–116. 2007. View Article : Google Scholar : PubMed/NCBI
22	Corone P, Bonaiti C, Feingold J, Fromont S and Berthet-Bondet D: Familial congenital heart disease: how are the various types related? Am J Cardio. 51:942–945. 1983. View Article : Google Scholar : PubMed/NCBI
23	Shillingford AJ and Weiner S: Maternal issues affecting the fetus. Clin Perinatol. 28:31–70. 2001. View Article : Google Scholar : PubMed/NCBI
24	Martínez-Frías ML, Bermejo E, Rodríguez-Pinilla E and Frías JL: Risk for congenital anomalies associated with different sporadic and daily doses of alcohol consumption during pregnancy: a case-control study. Birth Defects Res A Clin Mol Teratol. 70:194–200. 2004.PubMed/NCBI
25	Torfs CP and Christianson RE: Maternal risk factors and major associated defects in infants with Down syndrome. Epidemiology. 10:264–270. 1999. View Article : Google Scholar : PubMed/NCBI
26	Källén K: Maternal smoking and congenital heart defects. Eur J Epidomiol. 15:731–737. 1999.