Impact of a 22q11.2 Microdeletion on Adult All-Cause Mortality in Tetralogy of Fallot Patients.

Adult Cause of Death / trends Chromosome Deletion Chromosomes, Human, Pair 22 / genetics Female Humans Male Ontario / epidemiology Retrospective Studies Survival Rate / trends Tetralogy of Fallot / genetics Young Adult

Journal

The Canadian journal of cardiology
ISSN: 1916-7075
Titre abrégé: Can J Cardiol
Pays: England
ID NLM: 8510280

Informations de publication

Date de publication:
07 2020
Historique:
received: 07 03 2020
revised: 08 04 2020
accepted: 20 04 2020
pubmed: 30 4 2020
medline: 19 5 2021
entrez: 30 4 2020
Statut: ppublish

Résumé

Because of the importance of identifying factors that affect late outcomes in the increasing population of those with tetralogy of Fallot (TOF), we aimed to determine the effect of a 22q11.2 microdeletion on adult mortality, while accounting for pulmonary atresia, known to be enriched in 22q11.2 deletion syndrome (22q11.2DS). We studied 612 individuals with TOF recruited as adults at a single centre, 80 (13.1%) with molecularly confirmed 22q11.2 deletions and 532 without 22q11.2DS, followed for a total of 5961.3 person-years. Using a case-control design, Cox proportional hazard regression and Kaplan-Meier curves, we evaluated the effect of a 22q11.2 deletion on mortality and survival. All-cause mortality was 1.87% per person-year in the 22q11.2DS-TOF group and 0.80% in the other-TOF group. The presence of a 22q11.2 microdeletion was a significant predictor of adult mortality in TOF (hazard ratio, 5.00; P < 0.0001), after accounting for pulmonary atresia (hazard ratio, 2.71; P = 0.0106) and other factors. Overall, individuals with 22q11.2DS died on average 17.7 years earlier (P = 0.0055) than others with TOF, predominantly of cardiovascular causes, with proportionately more sudden cardiac deaths in those with 22q11.2DS-TOF (n = 5 [38.5%] vs n = 5 [11.9%], other-TOF; P = 0.0447). Kaplan-Meier curves showed reduced survival for those with 22q11.2DS (P < 0.0001); probability of survival to age 45 years, without pulmonary atresia, was 72% (22q11.2DS-TOF) and 98% (other-TOF). The results suggest that the 22q11.2 deletion significantly contributes to premature mortality in adults with TOF, mediated only in part by greater anatomic complexity. The interpretation of late outcome data in TOF will likely benefit from further genetic subtyping.

Sections du résumé

BACKGROUND
Because of the importance of identifying factors that affect late outcomes in the increasing population of those with tetralogy of Fallot (TOF), we aimed to determine the effect of a 22q11.2 microdeletion on adult mortality, while accounting for pulmonary atresia, known to be enriched in 22q11.2 deletion syndrome (22q11.2DS).
METHODS
We studied 612 individuals with TOF recruited as adults at a single centre, 80 (13.1%) with molecularly confirmed 22q11.2 deletions and 532 without 22q11.2DS, followed for a total of 5961.3 person-years. Using a case-control design, Cox proportional hazard regression and Kaplan-Meier curves, we evaluated the effect of a 22q11.2 deletion on mortality and survival.
RESULTS
All-cause mortality was 1.87% per person-year in the 22q11.2DS-TOF group and 0.80% in the other-TOF group. The presence of a 22q11.2 microdeletion was a significant predictor of adult mortality in TOF (hazard ratio, 5.00; P < 0.0001), after accounting for pulmonary atresia (hazard ratio, 2.71; P = 0.0106) and other factors. Overall, individuals with 22q11.2DS died on average 17.7 years earlier (P = 0.0055) than others with TOF, predominantly of cardiovascular causes, with proportionately more sudden cardiac deaths in those with 22q11.2DS-TOF (n = 5 [38.5%] vs n = 5 [11.9%], other-TOF; P = 0.0447). Kaplan-Meier curves showed reduced survival for those with 22q11.2DS (P < 0.0001); probability of survival to age 45 years, without pulmonary atresia, was 72% (22q11.2DS-TOF) and 98% (other-TOF).
CONCLUSIONS
The results suggest that the 22q11.2 deletion significantly contributes to premature mortality in adults with TOF, mediated only in part by greater anatomic complexity. The interpretation of late outcome data in TOF will likely benefit from further genetic subtyping.

Identifiants

DOI: 10.1016/j.cjca.2020.04.019 PMID: 32348848
pubmed: 32348848
pii: S0828-282X(20)30404-9
doi: 10.1016/j.cjca.2020.04.019
pii:
doi:

Types de publication

Journal Article Multicenter Study Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

1091-1097

Commentaires et corrections

Type : CommentIn

Informations de copyright

Crown Copyright © 2020. Published by Elsevier Inc. All rights reserved.

Auteurs

Spencer van Mil (S)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada.

Tracy Heung (T)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada.

Sarah Malecki (S)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada.

Lily Van (L)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada.

Janis Chang (J)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada.

Elemi Breetvelt (E)

Department of Psychiatry, The Hospital for Sick Children, Toronto, Ontario, Canada.

Rachel Wald (R)

Toronto Congenital Cardiac Centre for Adults, Division of Cardiology at the Peter Munk Cardiac Centre, Department of Medicine, University Health Network; and University of Toronto, Toronto, Ontario, Canada.

Erwin Oechslin (E)

The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada; Toronto Congenital Cardiac Centre for Adults, Division of Cardiology at the Peter Munk Cardiac Centre, Department of Medicine, University Health Network; and University of Toronto, Toronto, Ontario, Canada.

Candice Silversides (C)

The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada; Toronto Congenital Cardiac Centre for Adults, Division of Cardiology at the Peter Munk Cardiac Centre, Department of Medicine, University Health Network; and University of Toronto, Toronto, Ontario, Canada.

Anne S Bassett (AS)

Clinical Genetics Research Program, Centre for Addiction and Mental Health, Toronto, Ontario, Canada; The Dalglish Family 22q Clinic, University Health Network, Toronto, Ontario, Canada; Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada; Toronto Congenital Cardiac Centre for Adults, Division of Cardiology at the Peter Munk Cardiac Centre, Department of Medicine, University Health Network; and University of Toronto, Toronto, Ontario, Canada; Toronto General Hospital Research Institute and Campbell Family Mental Health Research Institute, Toronto, Ontario, Canada. Electronic address: anne.bassett@utoronto.ca.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Cause de décès › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Phénomènes génétiques › Ploïdies › Aneuploïdie › Monosomie › Délétion de segment de chromosome › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Chromosomes › Chromosomes de mammifère › Chromosomes humains › Chromosomes humains 21-22 et Y › Chromosomes humains de la paire 22 › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Régions géographiques › Amériques › Amérique du Nord › Canada › Ontario › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Caractéristiques des études épidémiologiques › Études épidémiologiques › Études de cohortes › Études rétrospectives › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Méthodes épidémiologiques › Collecte de données › Registre civil › Mortalité › Taux de survie › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Malformations et maladies congénitales, héréditaires et néonatales › Malformations › Malformations cardiovasculaires › Cardiopathies congénitales › Tétralogie de Fallot › Impact of a 22q11.2 Microdeletion on Adult...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › Jeune adulte › Impact of a 22q11.2 Microdeletion on Adult...