Review
Cardiovascular Anomalies Associated With Chromosome 22q11.2 Deletion Syndrome

https://doi.org/10.1016/j.amjcard.2010.01.333Get rights and content

Cardiovascular anomalies are present in 80% of neonates with 22q11.2 deletion syndrome. Three genes in chromosome 22q11.2 (TBX1, CRKL, and ERK2) have been identified whose haploinsufficiency causes dysfunction of the neural crest cell and anterior heart field and anomalies of 22q11.2 deletion syndrome. The most common diseases are conotruncal anomalies, which include tetralogy of Fallot (TF), TF with pulmonary atresia, truncus arteriosus, and interrupted aortic arch. A high prevalence of the deletion is noted in patients with TF with absent pulmonary valve, TF associated with pulmonary atresia and major aortopulmonary collateral arteries, truncus arteriosus, and type B interruption of aortic arch. Right aortic arch, aberrant subclavian artery, cervical origin of the subclavian artery, crossing pulmonary arteries, and major aortopulmonary collateral arteries are frequently associated with cardiovascular anomalies associated with 22q11.2 deletion syndrome. Virtually every type of congenital heart defect has been described early in the context of a 22q11.2 deletion. In conclusion, conotruncal anomaly associated with aortic arch and ductus arteriosus anomalies should increase the suspicion of 22q11.2 deletion.

Section snippets

Incidence

It should be noted that the overall estimate of how many patients with 22q11.2 deletions have congenital heart defects is likely biased with respect to (1) the degree to which asymptomatic patients with chromosomal deletions have been screened for associated aortic arch anomalies and (2) the biased ascertainment of affected infants but with the probable lack of ascertainment of minimally affected adults, that is, until they have affected children.

The largest series of 22q11.2 DS was reported by

Acknowledgment

Editorial help with this report from Joel S. Branch, Shonan Kamakura General Hospital, is much appreciated.

References (97)

  • L.M. Beauchesne et al.

    Prevalence and clinical manifestations of 22q11.2 microdeletion in adults with selected conotruncal anomalies

    J Am Coll Cardiol

    (2005)
  • W.L.A. Fung et al.

    Extracardiac features predicting 22q11.2 deletion syndrome in adult congenital heart disease

    Int J Cardiol

    (2008)
  • S.A. Webber et al.

    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

    (1996)
  • M.C. Johnson et al.

    Deletion within chromosome 22 is common in patients with absent pulmonary valve syndrome

    Am J Cardiol

    (1995)
  • K. Momma et al.

    Tetralogy of Fallot with pulmonary atresia associated with chromosome 22q11 deletion

    J Am Coll Cardiol

    (1996)
  • K. Momma et al.

    Tetralogy of Fallot associated with chromosome 22q11 deletion

    Am J Cardiol

    (1995)
  • W.T. Mahle et al.

    Deletion of chromosome 22q11.2 and outcome in patients with pulmonary atresia and ventricular septal defect

    Ann Thorac Surg

    (2003)
  • A. Carotti et al.

    Influence of chromosome 22q11.2 microdeletion on surgical outcome after treatment of tetralogy of Fallot with pulmonary atresia

    J Thorac Cardiovasc Surg

    (2003)
  • R. Rauch et al.

    Cervical origin of the subclavian artery as a specific marker for monosomy 22q11

    Am J Cardiol

    (2002)
  • R. Van Praagh et al.

    The anatomy of common aortopulmonary trunk (truncus arteriosus communis) and its embryologic implications: a study of 57 autopsied cases

    Am J Cardiol

    (1965)
  • K. Momma et al.

    Truncus arteriosus communis associated with chromosome 22q11 deletion

    J Am Coll Cardiol

    (1997)
  • K.L. Jue et al.

    Anomalous origins of pulmonary arteries from pulmonary trunk (“crossed pulmonary arteries”)

    Am Heart J

    (1966)
  • M.B. Lewin et al.

    A genetic etiology for interruption of the aortic arch type B

    Am J Cardiol

    (1997)
  • B. Marino et al.

    Deletion 22q11 in patient with interrupted aortic arch

    Am J Cardiol

    (1999)
  • K. Momma et al.

    Cardiac anomalies associated with chromosome 22q11 deletion in patients with conotruncal anomaly face syndrome

    Am J Cardiol

    (1996)
  • S. Melchionda et al.

    Transposition of the great arteries associated with deletion of chromosome 22q11

    Am J Cardiol

    (1995)
  • M.W. Consevage et al.

    Association of a mosaic chromosomal 22q11 deletion with hypoplastic left heart syndrome

    Am J Cardiol

    (1996)
  • D.B. McElhinney et al.

    Association of chromosome 22q11 deletion with isolated anomalies of aortic arch laterality and branching

    J Am Coll Cardiol

    (2001)
  • T.R. Johnson et al.

    Cardiac magnetic resonance imaging for accurate diagnosis of aortic arch anomalies in patients with 22q11.2 deletion

    Am J Cardiol

    (2005)
  • A. Kumar et al.

    Deletions in chromosome 22q11 region in cervical aortic arch

    Am J Cardiol

    (1997)
  • M.C. Johnson et al.

    Anomalous origin of the right pulmonary artery from the aorta and CATCH 22 syndrome

    Ann Thorac Surg

    (1995)
  • H. Dodo et al.

    Anomalous origin of the left main pulmonary artery from the ascending aorta associated with DiGeorge syndrome

    Am J Cardiol

    (1995)
  • M.R. Recto et al.

    Clinical implications of possible association of malposition of the branch pulmonary arteries with DiGeorge syndrome and microdeletion of chromosomal region 22q11

    Am J Cardiol

    (1997)
  • A.M. DiGeorge

    Discussions on a new concept of the cellular basis of immunity

    J Pediatr

    (1965)
  • R.J. Shprintzen et al.

    A new syndrome involving cleft palate, cardiac anomalies, typical faces, and learning disabilities

    Cleft Palate J

    (1978)
  • A. Kinouchi et al.

    Facial appearance of patients with conotruncal anomalies

    Jpn Pediatr

    (1976)
  • A. Takao et al.

    Cardiovascular malformations in the conotruncal anomaly face syndrome

  • A. Takao et al.

    Etiologic categorization of common heart disease

  • T. Shimizu et al.

    Conotruncal anomaly face syndrome: its heterogeneity and association with thymic involution

  • D.I. Wilson et al.

    DiGeorge syndrome with isolated aortic coarctation and isolated ventricular septal defect in three sibs with a 22q11 deletion of maternal origin

    Br Heart J

    (1991)
  • J. Burn et al.

    Conotruncal anomaly face syndrome is associated with a deletion within chromosome 22q11

    J Med Genet

    (1993)
  • M.E. Pierpont et al.

    Genetic basis for congenital heart defects: current knowledge

    Circulation

    (2007)
  • D.I. Wilson et al.

    DiGeorge syndrome: part of CATCH 22

    J Med Genet

    (1993)
  • L.H.S. Van Mierop et al.

    Cardiovascular anomalies in DiGeorge syndrome and importance of neural crest as a possible pathogenetic factor

    Am J Cardiol

    (1986)
  • M. Buckingham et al.

    Building the mammalian heart from two sources of myocardial cells

    Nat Rev Genet

    (2005)
  • C.S. Le Lievre et al.

    Mesenchymal derivatives of the neural crestAnalysis of chimeric quail and chick embryos

    J Embryol Exp Morphol

    (1975)
  • B.H. Hall

    The Neural Crest and Neural Crest Cells in Vertebrate Development and Evolution

  • M. Nishibatake et al.

    Pathogenesis of persistent truncus arteriosus and dextroposed aorta in the chick embryo after neural crest ablation

    Circulation

    (1987)
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    This study was supported by a grant from the Japanese Promotion Society for Cardiovascular Diseases, Tokyo, Japan.

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