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22q11.2 Deletion Syndrome is under-recognised in adult patients with tetralogy of Fallot and pulmonary atresia
  1. Klaartje van Engelen1,2,6,
  2. Ana Topf3,
  3. Bernard D Keavney3,
  4. Judith A Goodship3,
  5. Enno T van der Velde4,
  6. Marieke J H Baars2,
  7. Simone Snijder2,
  8. Antoon F Moorman5,
  9. Alex V Postma5,
  10. Barbara J M Mulder1,6
  1. 1Department of Cardiology, Academic Medical Center, Amsterdam, The Netherlands
  2. 2Department of Clinical Genetics, Academic Medical Center, Amsterdam, The Netherlands
  3. 3Institute of Human Genetics, Newcastle University, Newcastle upon Tyne, UK
  4. 4Department of Cardiology, Leiden University Medical Center, Leiden, The Netherlands
  5. 5Heart Failure Research Center, Department of Anatomy and Embryology, Academic Medical Center, Amsterdam, The Netherlands
  6. 6Interuniversity Cardiology Institute of the Netherlands, Utrecht, The Netherlands
  1. Correspondence to Dr K van Engelen, Department of Cardiology, Academic Medical Center, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands; k.vanengelen{at}


Background Three quarters of patients with 22q11.2 Deletion Syndrome (22q11.2DS) have congenital heart disease (CHD), typically conotruncal heart defects. Although it is currently common practice to test all children with typical CHD for 22q11.2DS, many adult patients have not been tested in the past and therefore 22q11.2DS might be under-recognised in adults.

Objectives To determine the prevalence of 22q11.2DS in adults with tetralogy of Fallot (TOF) and pulmonary atresia (PA)/ventricular septal defect (VSD) and to assess the level of recognition of the syndrome in adult patients.

Methods Patients were identified from CONCOR, a nationwide registry for adult patients with CHD. Inclusion criteria were diagnosis of TOF or PA/VSD and the availability of DNA. Patients with syndromes other than 22q11.2DS were excluded. Multiplex ligation-dependent probe amplification was used to detect 22q11.2 microdeletions.

Results 479 patients with TOF and 79 patients with PA/VSD (56% male, median age 34.7 years) were included and analysed. Twenty patients were already known to have 22q11.2DS. A 22q11.2 microdeletion was detected in a further 24 patients. Thirty-one patients with TOF (6.5%) had 22q11.2DS, whereas 13 patients with PA/VSD had 22q11.2DS (16.5%). Of all 22q11.2 microdeletions, 54% (24/44) were unknown before this study.

Conclusion This study shows that although the prevalence of 22q11.2DS in adults with TOF and PA/VSD is substantial, it is unrecognised in more than half of patients. As the syndrome has important clinical and reproductive implications, a diagnostic test should be considered in all adult patients with TOF and PA/VSD.

  • 22q11.2 Deletion syndrome
  • genetics
  • pulmonary atresia
  • syndrome
  • tetralogy of Fallot

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  • Funding Funding for this study was provided under the European Community's Sixth Framework program contract (HeartRepair LSHM-CT-2005-018630).

  • Competing interests None.

  • Ethics approval The CONCOR national registry obtained approval from a Central Medical Ethics Committee in the Netherlands for research studies performed on medical data and DNA of registered patients. No additional approval for this specific study was applied for.

  • Provenance and peer review Not commissioned; externally peer reviewed.

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