CLINICAL STUDIES
Frequency of 22q11 deletions in patients with conotruncal defects
Elizabeth Goldmuntz, MD, FACCa ,
Bernard J. Clark, MD, FACCa,
Laura E. Mitchell, PhD ,
Abbas F. Jawad, PhD ,
Bettina F. Cuneo, MD, FACC¶,
Lori Reed,
Donna McDonald-McGinn,
Peggy Chien,
Jennifer Feuer,
Elaine H. Zackai, MD ||,
Beverly S. Emanuel, PhD and
Deborah A. Driscoll, MD ||
a Division of Cardiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Division of Biostatistics and Epidemiology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia, Philadelphia, PA, USA
Department of Pediatrics, University of Pennsylvania Medical Center, Philadelphia, PA, USA
|| Department of Obstetrics and Gynecology, University of Pennsylvania Medical Center, Philadelphia, PA, USA
¶ The Heart Institute for Children, Hope Children’s Hospital, Oak Lawn, IL, USA
Manuscript received June 3, 1997;
revised manuscript received April 3, 1998,
accepted April 23, 1998.
Address for correspondence to: Elizabeth Goldmuntz, MD, Division of Cardiology, Department of Pediatrics, The Children’s Hospital of Philadelphia, 34th Street & Civic Center Blvd., Philadelphia, PA, USA 19104
goldmuntz{at}email.chop.edu
Objectives. This study was designed to determine the frequency of 22q11 deletions in a large, prospectively ascertained sample of patients with conotruncal defects and to evaluate the deletion frequency when additional cardiac findings are also considered.
Background. Chromosome 22q11 deletions are present in the majority of patients with DiGeorge, velocardiofacial and conotruncal anomaly face syndromes in which conotruncal defects are a cardinal feature. Previous studies suggest that a substantial number of patients with congenital heart disease have a 22q11 deletion.
Methods. Two hundred fifty-one patients with conotruncal defects were prospectively enrolled into the study and screened for the presence of a 22q11 deletion.
Results. Deletions were found in 50.0% with interrupted aortic arch (IAA), 34.5% of patients with truncus arteriosus (TA), and 15.9% with tetralogy of Fallot (TOF). Two of 6 patients with a posterior malalignment type ventricular septal defect (PMVSD) and only 1 of 20 patients with double outlet right ventricle were found to have a 22q11 deletion. None of the 45 patients with transposition of the great arteries had a deletion. The frequency of 22q11 deletions was higher in patients with anomalies of the pulmonary arteries, aortic arch or its major branches as compared to patients with a normal left aortic arch regardless of intracardiac anatomy.
Conclusions. A substantial proportion of patients with IAA, TA, TOF and PMVSD have a deletion of chromosome 22q11. Deletions are more common in patients with aortic arch or vessel anomalies. These results begin to define guidelines for deletion screening of patients with conotruncal defects.
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Abbreviations and Acronyms
| | CTAFS | = conotruncal anomaly face syndrome | | DGCR | = DiGeorge chromosomal region | | DGS | = DiGeorge syndrome | | DOLV | = double outlet left ventricle | | DORV | = double outlet right ventricle | | FISH | = fluorescence in situ hybridization | | IAA | = interrupted aortic arch | | PMVSD | = posterior malalignment type ventricular septal defect | | TGA | = transposition of the great arteries | | TA | = truncus arteriosus | | TOF | = tetralogy of Fallot | | VCFS | = velocardiofacial syndrome |
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85(1):
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|
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|
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|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
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115(23):
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|
|
|
|
|
|
|
T. Karamlou
Reply
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83(6):
2262 - 2263.
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|
|
|
|
|
|
|
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115(14):
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[Full Text]
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|
|
|
|
|
|
|
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82(2):
e11 - e13.
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|
|
|
|
|
|
|
M. A. Padula and A. M. Ades
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7(7):
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|
|
|
|
|
|
|
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|
|
|
|
|
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|
|
|
|
|
|
|
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|
|
|
|
|
|
|
N. Amabile, O. Ghez, F. Aubert, C. Ovaert, A. Fraisse, B. Kreitmann, and D. Metras
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|
|
|
|
|
|
|
J. A. Epstein and M. S. Parmacek
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112(4):
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|
|
|
|
|
|
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132(14):
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|
|
|
|
|
|
|
L. B. Pauliks, K.-C. Chan, A. Lorts, E. R. Elias, R. O. Cayre, and L. M. Valdes-Cruz
Shprintzen-Goldberg Syndrome With Tetralogy of Fallot and Subvalvar Aortic Stenosis
J. Ultrasound Med.,
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24(5):
703 - 706.
[Full Text]
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|
|
|
|
|
|
|
L. M. Beauchesne, C. A. Warnes, H. M. Connolly, N. M. Ammash, M. Grogan, S. M. Jalal, and V. V. Michels
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45(4):
595 - 598.
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|
|
|
|
|
|
|
R. A. Winn, E. D. Chan, E. L. Langmack, C. Kotaru, and E. Aronsen
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November 1, 2004;
126(5):
1694 - 1697.
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|
|
|
|
|
|
|
P. J. Gruber and J. A. Epstein
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Circ. Res.,
February 20, 2004;
94(3):
273 - 283.
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[Full Text]
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|
|
|
|
|
|
|
N. Muncke, C. Jung, H. Rudiger, H. Ulmer, R. Roeth, A. Hubert, E. Goldmuntz, D. Driscoll, J. Goodship, K. Schon, et al.
Missense Mutations and Gene Interruption in PROSIT240, a Novel TRAP240-Like Gene, in Patients With Congenital Heart Defect (Transposition of the Great Arteries)
Circulation,
December 9, 2003;
108(23):
2843 - 2850.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P Volpe, D Paladini, M Marasini, A L Buonadonna, M G Russo, G Caruso, A Marzullo, M Vassallo, P Martinelli, and M Gentile
Common arterial trunk in the fetus: characteristics, associations, and outcome in a multicentre series of 23 cases
Heart,
December 1, 2003;
89(12):
1437 - 1441.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. McElhinney, D. A. Driscoll, E. R. Levin, A. F. Jawad, B. S. Emanuel, and E. Goldmuntz
Chromosome 22q11 Deletion in Patients With Ventricular Septal Defect: Frequency and Associated Cardiovascular Anomalies
Pediatrics,
December 1, 2003;
112(6):
e472 - 476.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. McElhinney, E. Geiger, J. Blinder, D. Woodrow Benson, and E. Goldmuntz
NKX2.5 mutations in patients with congenital heart disease
J. Am. Coll. Cardiol.,
November 5, 2003;
42(9):
1650 - 1655.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. D. Botto, K. May, P. M. Fernhoff, A. Correa, K. Coleman, S. A. Rasmussen, R. K. Merritt, L. A. O'Leary, L.-Y. Wong, E. M. Elixson, et al.
A Population-Based Study of the 22q11.2 Deletion: Phenotype, Incidence, and Contribution to Major Birth Defects in the Population
Pediatrics,
July 1, 2003;
112(1):
101 - 107.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H H Hovels-Gurich, K Konrad, M Wiesner, R Minkenberg, B Herpertz-Dahlmann, B J Messmer, and G von Bernuth
Long term behavioural outcome after neonatal arterial switch operation for transposition of the great arteries
Arch. Dis. Child.,
December 1, 2002;
87(6):
506 - 510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. McElhinney, I. D. Krantz, L. Bason, D. A. Piccoli, K. M. Emerick, N. B. Spinner, and E. Goldmuntz
Analysis of Cardiovascular Phenotype and Genotype-Phenotype Correlation in Individuals With a JAG1 Mutation and/or Alagille Syndrome
Circulation,
November 12, 2002;
106(20):
2567 - 2574.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. H. Hovels-Gurich, M.-C. Seghaye, R. Schnitker, M. Wiesner, W. Huber, R. Minkenberg, F. Kotlarek, B. J. Messmer, and G. von Bernuth
Long-term neurodevelopmental outcomes in school-aged children after neonatal arterial switch operation
J. Thorac. Cardiovasc. Surg.,
September 1, 2002;
124(3):
448 - 458.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. A. Epstein, D. J. Rader, and M. S. Parmacek
Perspective: Cardiovascular Disease in the Postgenomic Era--Lessons Learned and Challenges Ahead
Endocrinology,
June 1, 2002;
143(6):
2045 - 2050.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A.D. GITLER, C.B. BROWN, L. KOCHILAS, J. LI, and J.A. EPSTEIN
Neural Crest Migration and Mouse Models of Congenital Heart Disease
Cold Spring Harb Symp Quant Biol,
January 1, 2002;
67(0):
57 - 62.
[Abstract]
[PDF]
|
|
|
|
|
|
|
W. Gong, S. Gottlieb, J. Collins, A. Blescia, H. Dietz, E. Goldmuntz, D. M McDonald-McGinn, E. H Zackai, B. S Emanuel, D. A Driscoll, et al.
Mutation analysis of TBX1 in non-deleted patients with features of DGS/VCFS or isolated cardiovascular defects
J. Med. Genet.,
December 1, 2001;
38
(12):
e45 - e45.
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Goldmuntz, E. Geiger, and D. W. Benson
NKX2.5 Mutations in Patients With Tetralogy of Fallot
Circulation,
November 20, 2001;
104(21):
2565 - 2568.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
L. Feiner, A. L. Webber, C. B. Brown, M. M. Lu, L. Jia, P. Feinstein, P. Mombaerts, J. A. Epstein, and J. A. Raper
Targeted disruption of semaphorin 3C leads to persistent truncus arteriosus and aortic arch interruption
Development,
August 15, 2001;
128(16):
3061 - 3070.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Henwood, C. Pickard, J. P Leek, C. P Bennett, Y. J Crow, J. D R Thompson, M. Ahmed, K. G Watterson, J. M Parsons, E. Roberts, et al.
A region of homozygosity within 22q11.2 associated with congenital heart disease: recessive DiGeorge/velocardiofacial syndrome?
J. Med. Genet.,
August 1, 2001;
38(8):
533 - 536.
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. B. McElhinney, B. J. Clark III, P. M. Weinberg, M. L. Kenton, D. McDonald-McGinn, D. A. Driscoll, E. H. Zackai, and E. Goldmuntz
Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching
J. Am. Coll. Cardiol.,
June 15, 2001;
37(8):
2114 - 2119.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. C. Bellinger, D. Wypij, A. J. du Plessis, L. A. Rappaport, J. Riviello, R. A. Jonas, and J. W. Newburger
Developmental and neurologic effects of alpha-stat versus pH-stat strategies for deep hypothermic cardiopulmonary bypass in infants
J. Thorac. Cardiovasc. Surg.,
February 1, 2001;
121(2):
0374 - 383.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schreiber, A. Eicken, G. Balling, M. Wottke, G. Schumacher, S. Un Paek, H. Meisner, J. Hess, and R. Lange
Single centre experience on primary correction of common arterial trunk: overall survival and freedom from reoperation after more than 15 years
Eur. J. Cardiothorac. Surg.,
July 1, 2000;
18(1):
68 - 73.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Schreiber, V. T. Tsang, R. Yates, S. Khambadkone, S. Yen Ho, and R. H. Anderson
Common arterial trunk associated with double aortic arch
Ann. Thorac. Surg.,
November 1, 1999;
68(5):
1850 - 1852.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Yamagishi, V. Garg, R. Matsuoka, T. Thomas, and D. Srivastava
A Molecular Pathway Revealing a Genetic Basis for Human Cardiac and Craniofacial Defects
Science,
February 19, 1999;
283(5405):
1158 - 1161.
[Abstract]
[Full Text]
|
|
|
|
