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A region of homozygosity within 22q11.2 associated with congenital heart disease: recessive DiGeorge/velocardiofacial syndrome?
  1. Judy Henwooda,
  2. Chris Pickarda,
  3. Jack P Leeka,
  4. Christopher P Bennettb,
  5. Yanick J Crowa,
  6. John D R Thompsonc,
  7. Mushtaq Ahmedb,
  8. Kevin G Wattersonc,
  9. Jonathan M Parsonsc,
  10. Emma Robertsa,
  11. Nicholas J Lench*,a
  1. aMolecular Medicine Unit, St James's University Hospital, Beckett Street, Leeds LS9 7TF, UK, bDepartment of Clinical Genetics, St James's University Hospital, Leeds, UK, cDepartment of Paediatric Cardiology, Yorkshire Heart Centre, The General Infirmary, Leeds, UK
  1. Dr Henwood,medjah{at}

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Editor—DiGeorge syndrome (DGS, MIM 18840) and velocardiofacial syndrome (VCFS, MIM 192430) are associated with interstitial deletions of chromosome 22q11.2 and are considered to be phenotypic variations of the same underlying genetic defect. Studies of patients with diagnoses of DGS or VCFS have estimated that between 68% and 88% have 22q11.2 microdeletions detectable by fluorescence in situ hybridisation.(FISH).1-3 Most of the deletions arise de novo, but data collected from a large group of patients estimated that 28% of deletions are inherited.4 Of subjects with a deletion, 90% have the same approximately 3 Mb region deleted, 7% have a nested 1.5 Mb deletion, and in other rare cases, unique deletions and translocations have been detected.5

The common clinical features associated with DGS/VCFS are congenital heart malformation, abnormal facies, thymic hypoplasia, cleft palate, and hypocalcaemia. However, despite the vast majority of patients diagnosed with DGS/VCFS having the same region of 22q11.2 deleted, there is wide phenotypic variation. The combination of symptoms can be so severe that the patient dies in the neonatal period or so mild that the condition is diagnosed only after the birth of a more severely affected child.4 6 7 It is estimated that deletions of 22q11.2 occur in 1 in 4000 live births, with 75% of patients harbouring the deletion having some form of congenital heart disease (CHD).4 7 Conotruncal heart defects most commonly found in DGS/VCFS patients with 22q11.2 deletions are interrupted aortic arch (IAA) type B, truncus arteriosus (TA), and tetralogy of Fallot (TOF).4 7 8 Furthermore, congenital conotruncal cardiac defects account for around 50% of cardiac malformations seen in the neonatal period9 and approximately 50% of patients with conotruncal cardiac malformations have been found to have deletions at 22q11.2.10-13

It is therefore reasonable to suspect DGS …

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  • * Present address: Oxagen Ltd, Abingdon, UK