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22q11.2 deletion syndrome as a risk factor for aortic root dilation in tetralogy of Fallot

Published online by Cambridge University Press:  10 April 2013

Anitha S. John ,
Jack Rychik ,
Munziba Khan ,
Wei Yang  and
Elizabeth Goldmuntz
Anitha S. John
Affiliation:
Division of Cardiology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC, United States of America Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
Jack Rychik
Affiliation:
Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
Munziba Khan
Affiliation:
Division of Cardiology, Children's National Medical Center, George Washington University School of Medicine, Washington, DC, United States of America
Wei Yang
Affiliation:
Division of Biostatistics, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
Elizabeth Goldmuntz*
Affiliation:
Division of Cardiology, The Children's Hospital of Philadelphia, University of Pennsylvania Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America
*
Correspondence to: Dr E. Goldmuntz, MD, Professor of Pediatrics, Children's Hospital of Philadelphia, Division of Cardiology, Abramson Research Center, 702A, 3615 Civic Center Boulevard, Philadelphia, PA 19104-4318, United States of America. Tel: 215 590 5820; Fax: 215 476 5700; E-mail: [email protected]
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Abstract

Background: Aortic root dilation has been observed in some patients with tetralogy of Fallot. This study examines whether 22q11.2 deletion is a risk factor for aortic root dilation in tetralogy of Fallot. Methods: Patients with tetralogy of Fallot, in the age group of 6–18 years, with defined deletion status and echocardiograms (2003–2009) were identified from research databases. The diameter at the aortic annulus, sinus, and sinotubular junction was measured and analysed as Z-scores. Variables were examined in univariate and multivariate regression analysis. Results: Of 171 patients, 66% were male, 16% had 22q11.2 deletion, 40% had an aortic arch anomaly, and 11% had both a 22q11.2 deletion and aortic arch anomaly. Echocardiograms were performed at a mean age of 12 + 3 years. More patients with 22q11.2 deletion had Z-scores >3 at the sinus diameter (45% versus 35%, p = 0.02). In the multivariate analysis, the combination of 22q11.2 deletion and aortic arch anomalies was associated with both aortic annular dilation (p = 0.006) and aortic sinus dilation (p = 0.05). In the subset with pulmonary valve atresia, similar findings were observed at the aortic annulus (Z-score of 4.6 versus 2.2, p = 0.05) and the sinuses (Z-score of 4.4 versus 2.7, p = 0.06). Male sex (p < 0.03) and pulmonary atresia (p < 0.006) were additional risk factors for dilation at the annulus and sinuses. Conclusions: Children with tetralogy of Fallot with 22q11.2 deletion and aortic arch anomalies have increased aortic annular and aortic sinus dilation. Further longitudinal study is needed to assess whether both features are associated with progressive aortic root dilation.

Keywords

22q11.2 deletion syndromeaortic root dilationtetralogy of Fallot
Type
Original Articles
Information
Cardiology in the Young , Volume 24 , Issue 2 , April 2014 , pp. 303 - 310
Copyright
Copyright © Cambridge University Press 2013 

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References

1. Perry, LW, Neill, CA, Ferencz, C. Infants with congenital heart disease: The cases. In: Ferencz C, Rubin JD, Loffredo CA, et al. (eds.). Perspectives in Pediatric Cardiology Epidemiology of Congenital Heart Disease, the Baltimore-Washington Infant Study 1981–1989. Futura Publishing, Armonk, NY, 1993, pp 33–62.Google Scholar
2. Nollert, G, Fischlein, T, Bouterwek, S, et al. Long-term survival in patients with repair of tetralogy of Fallot. J Am Coll Cardiol 1997; 30: 1374–1383.CrossRefGoogle ScholarPubMed
3. Niwa, K, Siu, S, Webb, G, et al. Progressive aortic root dilatation in adults late after repair of tetralogy of Fallot. Circulation 2002; 106: 1374–1378.Google Scholar
4. Goldmuntz, E. DiGeorge syndrome: new insights. Clin Perinatol 2005; 32: 963–978.Google Scholar
5. Momma, K, Kondo, C, Ando, M, et al. Tetralogy of Fallot associated with chromosome 22q11 deletion. J Am Coll Cardiol 1995; 76: 618–621.CrossRefGoogle ScholarPubMed
6. Marino, B, Digilio, MC, Grazioli, S, et al. Associated cardiac anomalies in isolated and syndromic patients with tetralogy of Fallot. J Am Coll Cardiol 1996; 77: 505–508.Google Scholar
7. Amati, F, Mari, A, Digilio, MC, et al. 22q11 deletions in isolated and syndromic patients with tetralogy of Fallot. Hum Genet 1995; 95: 479–482.Google Scholar
8. Goldmuntz, E, Clark, BJ, Mitchell, LE, et al. Frequency of 22q11 deletions in patients with conotruncal defects. J Am Coll Cardiol 1998; 32: 492–498.Google Scholar
9. Takahashi, K, Kido, S, Hoshino, K, et al. Frequency of a 22q11 deletion in patients with conotruncal cardiac malformations: a prospective study. Eur J Pediatr 1995; 154: 878–881.Google Scholar
10. John, AS, McDonald-McGinn, DM, Zakai, E, et al. Aortic root dilation in patients with 22q11 deletion syndrome. Am J Med GenetA 2009; 149A: 939–942.CrossRefGoogle ScholarPubMed
11. Dodds, GA III, Warnes, CA, Danielson, GK. Aortic valve replacement after repair of pulmonary atresia and ventricular septal defect or tetralogy of Fallot. J Thorac Cardiovasc Surg 1997; 113: 736–741.Google Scholar
12. Rathi, V, Doyle, M, Williams, R, et al. Massive aortic aneurism and dissection in repaired tetralogy of Fallot; diagnosis by cardiovascular magnetic resonance imaging. Int J Cardiol 2005; 101: 169–170.CrossRefGoogle Scholar
13. Roux, N, Doguet, F, Litzler, P, et al. Occurrence of an ascending aorta aneurysm 25 years after cure of a tetralogy of Fallot. J Card Surg 2008; 23: 163–164.CrossRefGoogle ScholarPubMed
14. Kim, W, Seo, J, Kim, S, et al. Aortic dissection late after repair of tetralogy of Fallot. Int J Cardiol 2005; 101: 515–516.Google Scholar
15. Miller, DT, Adam, MP, Aradhya, S, et al. Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet 2010; 86: 749–764.Google Scholar
16. Edwards, J. An atlas of acquired diseases of the heart and great vessels. WB Saunders, Philadelphia, 1948.Google Scholar
17. Allen, H, Driscoll, D, Shaddy, R, et al. eds. Aortic arch anomalies. Lippincott Williams & Wilkins, Philadelphia, 2008.Google Scholar
18. Bhat, AH, Smith, CJ, Hawker, RE. Late aortic root dilatation in tetralogy of Fallot may be prevented by early repair in infancy. Pediatr Cardiol 2004; 25: 654–659.CrossRefGoogle ScholarPubMed
19. Chong, WY, Wong, WH, Chiu, CS, et al. Aortic root dilation and aortic elastic properties in children after repair of tetralogy of Fallot. Am J Cardiol 2006; 97: 905–909.Google Scholar
20. Cheung, YF, Ou, X, Wong, SJ. Central and peripheral arterial stiffness in patients after surgical repair of tetralogy of Fallot: implications for aortic root dilatation. Heart 2006; 92: 1827–1830.Google Scholar
21. Senzaki, H, Iwamoto, Y, Ishido, H, et al. Arterial haemodynamics in patients after repair of tetralogy of Fallot: influence on left ventricular after load and aortic dilatation. Heart 2008; 94: 70–74.Google Scholar
22. Mahle, WT, Crisalli, J, Coleman, K, et al. Deletion of chromosome 22q11.2 and outcome in patients with pulmonary atresia and ventricular septal defect. Ann Thorac Surg 2003; 76: 567–571.CrossRefGoogle ScholarPubMed
23. Michielon, G, Marino, B, Formigari, R, et al. Genetic syndromes and outcome after surgical correction of tetralogy of Fallot. Ann Thorac Surg 2006; 81: 968–975.Google Scholar
24. Michielon, G, Marino, B, Oricchio, G, et al. Impact of DEL22q11, trisomy 21, and other genetic syndromes on surgical outcome of conotruncal heart defects. J Thorac Cardiovasc Surg 2009; 138: 565–570; e2.Google Scholar
25. Kiziltan, HT, Topcu, S, Ozbarlas, N, et al. Combined primary repair of tetralogy of Fallot and aortic root replacement. Ann Thorac Surg 2001; 72: 2124–2125.Google Scholar
26. Ishizaka, T, Ichikawa, H, Sawa, Y, et al. Prevalence and optimal management strategy for aortic regurgitation in tetralogy of Fallot. Eur J Cardiothorac Surg 2004; 26: 1080–1086.CrossRefGoogle ScholarPubMed
27. Tan, J, Gatzoulis, M, Ho, S. Aortic root disease in tetralogy of Fallot. Curr Opin Cardiol 2006; 21: 569–572.Google Scholar
28. Niwa, K, Perloff, JK, Bhuta, SM, et al. Structural abnormalities of great arterial walls in congenital heart disease: light and electron microscopic analyses. Circulation 2001; 103: 393–400.CrossRefGoogle ScholarPubMed
29. Cheung, YF, Hong, WJ, Chan, KW, et al. Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair. Int J Cardiol 2011; 151: 214–217.Google Scholar