Skip to main content

Advertisement

Log in

Investigating 22q11.2 Deletion and Other Chromosomal Aberrations in Fetuses With Heart Defects Detected by Prenatal Echocardiography

  • Original Article
  • Published:
Pediatric Cardiology Aims and scope Submit manuscript

Abstract

Congenital heart disease (CHD) is the most common birth defect and the leading cause of mortality in the first year of life. In fetuses with a heart defect, chromosomal abnormalities are very frequent. Besides aneuploidy, 22q11.2 deletion is one of the most recognizable chromosomal abnormalities causing CHD. The frequency of this abnormality varies in nonselected populations. This study aimed to investigate the incidence of the 22q11.2 deletion and other chromosomal alterations in a Brazilian sample of fetuses with structural cardiac anomalies detected by fetal echocardiography. In a prospective study, 68 fetuses with a heart defect were evaluated. Prenatal detection of cardiac abnormalities led to identification of aneuploidy or structural chromosomal anomaly in 35.3% of these cases. None of the fetuses with apparently normal karyotypes had a 22q11.2 deletion. The heart defects most frequently associated with chromosomal abnormalities were atrioventricular septal defect (AVSD), ventricular septal defect (VSD), and tetralogy of Fallot. Autosomal trisomies 18 and 21 were the most common chromosomal abnormalities. The study results support the strong association of chromosome alterations and cardiac malformation, especially in AVSD and VSD, for which a chromosome investigation is indicated. In fetuses with an isolated conotruncal cardiopathy, fluorescence in situ hybridization (FISH) to investigate a 22q11.2 deletion is not indicated.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Allan LD, Sharland GK, Milburn A, Lockhart SM, Groves AM, Anderson RH, Cook AC, Fagg NL (1994) Prospective diagnosis of 1, 006 consecutive cases of congenital heart disease in the fetus. J Am Coll Cardiol 23:1452–1458

    Article  CAS  PubMed  Google Scholar 

  2. Belangero SIN, Bellucco FTS, Kulikowski LD, Christofolini DM, Cernach MCSP, Melaragno MI (2009) 22q11.2 Deletion in patients with conotruncal heart defect and del22q syndrome phenotype. Arq Bras Cardiol 92:289–293

    Google Scholar 

  3. Boldt T, Andersson S, Eronen M (2002) Outcome of structural heart disease diagnosed in utero. Scand Cardiovasc J 36:73–79

    Article  PubMed  Google Scholar 

  4. Boudjemline Y, Fermont L, Le Bidois J, Lyonnet S, Sidi D, Bonnet D (2001) Prevalence of 22q11 deletion in fetuses with conotruncal cardiac defects: a 6-year prospective study. J Pediatr 138:520–524

    Article  CAS  PubMed  Google Scholar 

  5. Calcagni G, Digilio MC, Sarkozy A, Dallapiccola B, Marino B (2007) Familial recurrence of congenital heart disease: an overview and review of the literature. Eur J Pediatr 166:111–116

    Article  PubMed  Google Scholar 

  6. Chaoui R, Korner H, Bommer C, Goldner B, Bierlich A, Bollmann R (1999) Prenatal diagnosis of heart defects and associated chromosomal aberrations. Ultraschall Med 20:177–184

    Article  CAS  PubMed  Google Scholar 

  7. Comas Gabriel C, Galindo A, Martinez JM, Carrera JM, Gutierrez-Larraya F, de la Fuente P, Puerto B, Borrell A (2002) Early prenatal diagnosis of major cardiac anomalies in a high-risk population. Prenat Diagn 22:586–593

    Article  CAS  PubMed  Google Scholar 

  8. Daw SC, Taylor C, Kraman M, Call K, Mao J, Schuffenhauer S, Meitinger T, Lipson T, Goodship J, Scambler P (1996) A common region of 10p deleted in DiGeorge and velocardiofacial syndromes. Nat Genet 13:458–460

    Article  CAS  PubMed  Google Scholar 

  9. Debrus S, Berger G, de Meeus A, Sauer U, Guillaumont S, Voisin M, Bozio A, Demczuk S, Aurias A, Bouvagnet P (1996) Familial nonsyndromic conotruncal defects are not associated with a 22q11 microdeletion. Hum Genet 97:138–144

    Article  CAS  PubMed  Google Scholar 

  10. Digilio MC, Marino B, Giannotti A, Dallapiccola B (1997) Chromosome 22q11 microdeletion and isolated conotruncal heart defects. Arch Dis Child 76:79–80

    Article  CAS  PubMed  Google Scholar 

  11. Evans PR (1950) Cardiac anomalies in mongolism. Br Heart J 12:258–262

    Article  CAS  PubMed  Google Scholar 

  12. Ferencz C, Neill CA, Boughman JA, Rubin JD, Brenner JI, Perry LW (1989) Congenital cardiovascular malformations associated with chromosome abnormalities: an epidemiologic study. J Pediatr 114:79–86

    Article  CAS  PubMed  Google Scholar 

  13. Ferreres JC, Planas S, Martinez-Saez EA, Vendrell T, Peg V, Salcedo MT, Ramon YCS, Toran N (2008) Pathological findings in the complete trisomy 9 syndrome: three case reports and review of the literature. Pediatr Dev Pathol 11:23–29

    Article  PubMed  Google Scholar 

  14. Fokstuen S, Arbenz U, Artan S, Dutly F, Bauersfeld U, Brecevic L, Fasnacht M, Rothlisberger B, Schinzel A (1998) 22q11.2 Deletions in a series of patients with nonselective congenital heart defects: incidence, type of defects, and parental origin. Clin Genet 53:63–69

    Article  CAS  PubMed  Google Scholar 

  15. Furlanetto G, Binotto MA (2008) Tetralogia de Fallot. In: Croti UA, Mattos SS, Pinto VC Jr, Aiello VD (eds) Cardiologia e cirurgia cardiovascular pediátrica 2008. Roca, São Paulo, pp 291–310

    Google Scholar 

  16. Galindo A, Mendoza A, Arbues J, Graneras A, Escribano D, Nieto O (2009) Conotruncal anomalies in fetal life: accuracy of diagnosis, associated defects, and outcome. Eur J Obstet Gynecol Reprod Biol 146:55–60

    Article  CAS  PubMed  Google Scholar 

  17. Gembruch U, Baschat AA, Knopfle G, Hansmann M (1997) Results of chromosomal analysis in fetuses with cardiac anomalies as diagnosed by first- and early second-trimester echocardiography. Ultrasound Obstet Gynecol 10:391–396

    Article  CAS  PubMed  Google Scholar 

  18. Goldmuntz E, Clark BJ, Mitchell LE, Jawad AF, Cuneo BF, Reed L, McDonald-McGinn D, Chien P, Feuer J, Zackai EH, Emanuel BS, Driscoll DA (1998) Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 32:492–498

    Article  CAS  PubMed  Google Scholar 

  19. Hafner E, Scholler J, Schuchter K, Sterniste W, Philipp K (1998) Detection of fetal congenital heart disease in a low-risk population. Prenat Diagn 18:808–815

    Article  CAS  PubMed  Google Scholar 

  20. Hoffman JI (1995) Incidence of congenital heart disease: II. Prenatal incidence. Pediatr Cardiol 16:155–165

    Article  CAS  PubMed  Google Scholar 

  21. Hoffman JI, Kaplan S (2002) The incidence of congenital heart disease. J Am Coll Cardiol 39:1890–1900

    Article  PubMed  Google Scholar 

  22. Iserin L, de Lonlay P, Viot G, Sidi D, Kachaner J, Munnich A, Lyonnet S, Vekemans M, Bonnet D (1998) Prevalence of the microdeletion 22q11 in newborn infants with congenital conotruncal cardiac anomalies. Eur J Pediatr 157:881–884

    Article  CAS  PubMed  Google Scholar 

  23. Kidd SA, Lancaster PA, McCredie RM (1993) The incidence of congenital heart defects in the first year of life. J Paediatr Child Health 29:344–349

    Article  CAS  PubMed  Google Scholar 

  24. Manji S, Roberson JR, Wiktor A, Vats S, Rush P, Diment S, Van Dyke DL (2001) Prenatal diagnosis of 22q11.2 deletion when ultrasound examination reveals a heart defect. Genet Med 3:65–66

    Article  CAS  PubMed  Google Scholar 

  25. Marino B, Digilio MC (2000) Congenital heart disease and genetic syndromes: specific correlation between cardiac phenotype and genotype. Cardiovasc Pathol 9:303–315

    Article  CAS  PubMed  Google Scholar 

  26. Marino B, Vairo U, Corno A, Nava S, Guccione P, Calabro R, Marcelletti C (1990) Atrioventricular canal in Down syndrome: prevalence of associated cardiac malformations compared with patients without Down syndrome. Am J Dis Child 144:1120–1122

    CAS  PubMed  Google Scholar 

  27. Moore JW, Binder GA, Berry R (2004) Prenatal diagnosis of aneuploidy and deletion 22q11.2 in fetuses with ultrasound detection of cardiac defects. Am J Obstet Gynecol 191:2068–2073

    Article  CAS  PubMed  Google Scholar 

  28. Moorhead PS, Nowell PC, Mellman WJ, Battips DM, Hungerford DA (1960) Chromosome preparations of leukocytes cultured from human peripheral blood. Exp Cell Res 20:613–616

    Article  CAS  PubMed  Google Scholar 

  29. Musewe NN, Alexander DJ, Teshima I, Smallhorn JF, Freedom RM (1990) Echocardiographic evaluation of the spectrum of cardiac anomalies associated with trisomy 13 and trisomy 18. J Am Coll Cardiol 15:673–677

    Article  CAS  PubMed  Google Scholar 

  30. Nazareth HRS, Pinto W Jr, Andrade JAD (1981) Diagnóstico pré-natal de aberrações cromossômicas. Rev Brasil Genet IV:459–470

    Google Scholar 

  31. Paladini D, Tartaglione A, Agangi A, Teodoro A, Forleo F, Borghese A, Martinelli P (2000) The association between congenital heart disease and Down syndrome in prenatal life. Ultrasound Obstet Gynecol 15:104–108

    Article  CAS  PubMed  Google Scholar 

  32. Paladini D, Russo M, Teodoro A, Pacileo G, Capozzi G, Martinelli P, Nappi C, Calabro R (2002) Prenatal diagnosis of congenital heart disease in the Naples area during the years 1994–1999: the experience of a joint fetal-pediatric cardiology unit. Prenat Diagn 22:545–552

    Article  PubMed  Google Scholar 

  33. Pierpont ME, Basson CT, Benson DW Jr, Gelb BD, Giglia TM, Goldmuntz E, McGee G, Sable CA, Srivastava D, Webb CL (2007) 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 115:3015–3038

    Article  PubMed  Google Scholar 

  34. Pinkel D, Gray JW, Trask B, van den Engh G, Fuscoe J, van Dekken H (1986) Cytogenetic analysis by in situ hybridization with fluorescently labeled nucleic acid probes. Cold Spring Harb Symp Quant Biol 51(Pt 1):151–157

    CAS  PubMed  Google Scholar 

  35. Raymond FL, Simpson JM, Mackie CM, Sharland GK (1997) Prenatal diagnosis of 22q11 deletions: a series of five cases with congenital heart defects. J Med Genet 34:679–682

    Article  CAS  PubMed  Google Scholar 

  36. Raymond FL, Simpson JM, Sharland GK, Ogilvie Mackie CM (1997) Fetal echocardiography as a predictor of chromosomal abnormality. Lancet 350:930

    Article  CAS  PubMed  Google Scholar 

  37. Schuffenhauer S, Seidel H, Oechsler H, Belohradsky B, Bernsau U, Murken J, Meitinger T (1995) Di George syndrome and partial monosomy 10p: case report and review. Ann Genet 38:162–167

    CAS  PubMed  Google Scholar 

  38. Shaffer LG, Slovak ML, Campbell LJ (2009) International System for Human Cytogenetic Nomenclature (ISCN): recommendations of the International Standing Committee on Human Cytogenetic Nomenclature. S Karger Publishers, Basel, pp 1–128

  39. Tennstedt C, Chaoui R, Korner H, Dietel M (1999) Spectrum of congenital heart defects and extracardiac malformations associated with chromosomal abnormalities: results of a seven year necropsy study. Heart 82:34–39

    CAS  PubMed  Google Scholar 

  40. Thomas JA, Graham JM (1997) Chromosome 22q11 deletion syndrome: an update and review for the primary pediatrician. Clin Pediatr 36:253–266

    Article  CAS  Google Scholar 

  41. Van Esch H, Groenen P, Fryns JP, Van de Ven W, Devriendt K (1999) The phenotypic spectrum of the 10p deletion syndrome versus the classical DiGeorge syndrome. Genet Couns 10:59–65

    PubMed  Google Scholar 

  42. Webber SA, Hatchwell E, Barber JC, Daubeney PE, Crolla JA, Salmon AP, Keeton BR, Temple IK, Dennis NR (1996) Importance of microdeletions of chromosomal region 22q11 as a cause of selected malformations of the ventricular outflow tracts and aortic arch: a three-year prospective study. J Pediatr 129:26–32

    Article  CAS  PubMed  Google Scholar 

  43. Wimalasundera RC, Gardiner HM (2004) Congenital heart disease and aneuploidy. Prenat Diagn 24:1116–1122

    Article  CAS  PubMed  Google Scholar 

  44. Yates R (1999) Fetal cardiac abnormalities and their association with aneuploidy. Prenat Diagn 19:563–566

    Article  CAS  PubMed  Google Scholar 

  45. Yatsenko SA, Yatsenko AN, Szigeti K, Craigen WJ, Stankiewicz P, Cheung SW, Lupski JR (2004) Interstitial deletion of 10p and atrial septal defect in DiGeorge 2 syndrome. Clin Genet 66:128–136

    Article  CAS  PubMed  Google Scholar 

  46. Zielinsky P, Assad RS (2008) Cardiologia e cirurgia cardíaca fetal. In: Croti UA, Mattos SS, Pinto Jr VC, Aiello VD (eds) Cardiologia e cirurgia cardiovascular pediátrica 2008. Roca, São Paulo, pp 51–84

Download references

Acknowledgment

This work was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) and Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Maria Isabel Melaragno.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Bellucco, F.T.S., Belangero, S.I.N., Farah, L.M.S. et al. Investigating 22q11.2 Deletion and Other Chromosomal Aberrations in Fetuses With Heart Defects Detected by Prenatal Echocardiography. Pediatr Cardiol 31, 1146–1150 (2010). https://doi.org/10.1007/s00246-010-9763-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00246-010-9763-0

Keywords

Navigation