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J Med Genet 46:324-330 doi:10.1136/jmg.2008.063800
  • Original article

Premature death in adults with 22q11.2 deletion syndrome

  1. A S Bassett1,2,3,
  2. E W C Chow1,2,
  3. J Husted1,5,
  4. K A Hodgkinson1,4,
  5. E Oechslin3,
  6. L Harris3,
  7. C Silversides3
  1. 1
    Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada
  2. 2
    Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
  3. 3
    Toronto Congenital Cardiac Centre for Adults, University of Toronto, Peter Munk Cardiac Centre, University Health Network/Toronto General Hospital, Toronto, Ontario, Canada
  4. 4
    Department of Genetics, Memorial University of Newfoundland, Newfoundland, Canada
  5. 5
    Department of Health Studies, University of Waterloo, Waterloo, Ontario, Canada
  1. Dr A S Bassett, Centre for Addiction and Mental Health, 1001 Queen Street West, Toronto, Ontario M6J 1H4 Canada; anne.bassett{at}utoronto.ca
  • Received 9 October 2008
  • Revised 9 December 2008
  • Accepted 31 December 2008
  • Published Online First 25 February 2009

Abstract

Background: 22q11.2 deletion syndrome (22q11.2DS) is a multisystem disease with a prevalence of 1/4000. Variable expression of congenital and later onset features contributes to its under-recognition. Longevity in those surviving childhood is believed to be normal but data are limited.

Methods: We prospectively followed 264 subjects; 102 adults (>17 years) with 22q11.2DS (44 male (M), 58 female (F); mean (SD) age 33.6 (10.9) years) and their 162 unaffected siblings (77 M, 85 F; mean age 36.1 (12.2) years). We compared survival between groups using Kaplan–Meier estimates.

Results: Twelve (11.8%; 4 M, 8 F) individuals with 22q11.2DS and no siblings died (p<0.0001). Survival to ages 40 and 50 years was 89.9% and 73.9%, respectively. Median age at death was 41.5 (range 18.1–68.6) years. Deaths included two (7.7%) of 26 subjects with neither major congenital heart disease (CHD) nor schizophrenia. Four of six sudden and unexpected deaths occurred in individuals with no major CHD. There was no evidence of cancer or coronary artery disease or family history of sudden death in the 12 patients who died, six of whom had autopsies.

Discussion: Individuals with 22q11.2DS who survive childhood have diminished life expectancy and increased risk of sudden death not attributable to any single factor. Some sudden and/or premature deaths observed in the general population may represent undiagnosed 22q11.2DS. Increased recognition of the syndrome by family doctors, specialists and coroners will be essential to facilitate the tissue studies needed to determine underlying mechanisms.

Footnotes

  • Funding: This research was supported by grants from the Canadian Institutes of Health Research (MOP-79518), Medical Research Council of Canada (MOP-38099), W. Garfield Weston Foundation and Ontario Mental Health Foundation, and by a Distinguished Investigator Award from the National Alliance for Research on Schizophrenia and Depression (ASB) and Canada Research Chair in Schizophrenia Genetics (ASB).

  • Competing interests: None.

  • Patient consent: Obtained.