Cargando…

All-cause mortality and survival in adults with 22q11.2 deletion syndrome

PURPOSE: Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome. METHODS: We studied 309 well-characterized adults (age ≥17 years) with 22q11.2DS and their 1014 unaffected parents and sibl...

Descripción completa

Detalles Bibliográficos
Autores principales: Van, Lily, Heung, Tracy, Graffi, Justin, Ng, Enoch, Malecki, Sarah, Van Mil, Spencer, Boot, Erik, Corral, Maria, Chow, Eva W. C., Hodgkinson, Kathleen A., Silversides, Candice, Bassett, Anne S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group US 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774995/
https://www.ncbi.nlm.nih.gov/pubmed/30948858
http://dx.doi.org/10.1038/s41436-019-0509-y
_version_ 1783456139501895680
author Van, Lily
Heung, Tracy
Graffi, Justin
Ng, Enoch
Malecki, Sarah
Van Mil, Spencer
Boot, Erik
Corral, Maria
Chow, Eva W. C.
Hodgkinson, Kathleen A.
Silversides, Candice
Bassett, Anne S.
author_facet Van, Lily
Heung, Tracy
Graffi, Justin
Ng, Enoch
Malecki, Sarah
Van Mil, Spencer
Boot, Erik
Corral, Maria
Chow, Eva W. C.
Hodgkinson, Kathleen A.
Silversides, Candice
Bassett, Anne S.
author_sort Van, Lily
collection PubMed
description PURPOSE: Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome. METHODS: We studied 309 well-characterized adults (age ≥17 years) with 22q11.2DS and their 1014 unaffected parents and siblings, using a prospective case–control design. We used Cox proportional hazards regression modeling and Kaplan–Meier curves to investigate effects of the 22q11.2 deletion and its associated features on all-cause mortality and survival. RESULTS: The 22q11.2 deletion (hazard ratio [HR] 8.86, 95% CI 2.87–27.37) and major congenital heart disease (CHD; HR 5.03, 95% CI 2.27–11.17), but not intellectual disability or psychotic illness, were significant independent predictors of mortality for adults with 22q11.2DS compared with their siblings. Amongst those with 22q11.2DS, there were 31 deaths that occurred at a median age of 46.4 (range 18.1–68.6) years; a substantial minority had outlived both parents. Probability of survival to age 45 years was approximately 72% for those with major CHD, and 95% for those with no major CHD (p < 0.0001). CONCLUSION: For adults with 22q11.2DS, the 22q11.2 deletion and more severe forms of CHD both contribute to a lower life expectancy than family-based expectations. The results have implications for genetic counseling and anticipatory care.
format Online
Article
Text
id pubmed-6774995
institution National Center for Biotechnology Information
language English
publishDate 2019
publisher Nature Publishing Group US
record_format MEDLINE/PubMed
spelling pubmed-67749952019-10-04 All-cause mortality and survival in adults with 22q11.2 deletion syndrome Van, Lily Heung, Tracy Graffi, Justin Ng, Enoch Malecki, Sarah Van Mil, Spencer Boot, Erik Corral, Maria Chow, Eva W. C. Hodgkinson, Kathleen A. Silversides, Candice Bassett, Anne S. Genet Med Article PURPOSE: Given limited data available on long-term outcomes in 22q11.2 deletion syndrome (22q11.2DS), we investigated mortality risk in adults with this microdeletion syndrome. METHODS: We studied 309 well-characterized adults (age ≥17 years) with 22q11.2DS and their 1014 unaffected parents and siblings, using a prospective case–control design. We used Cox proportional hazards regression modeling and Kaplan–Meier curves to investigate effects of the 22q11.2 deletion and its associated features on all-cause mortality and survival. RESULTS: The 22q11.2 deletion (hazard ratio [HR] 8.86, 95% CI 2.87–27.37) and major congenital heart disease (CHD; HR 5.03, 95% CI 2.27–11.17), but not intellectual disability or psychotic illness, were significant independent predictors of mortality for adults with 22q11.2DS compared with their siblings. Amongst those with 22q11.2DS, there were 31 deaths that occurred at a median age of 46.4 (range 18.1–68.6) years; a substantial minority had outlived both parents. Probability of survival to age 45 years was approximately 72% for those with major CHD, and 95% for those with no major CHD (p < 0.0001). CONCLUSION: For adults with 22q11.2DS, the 22q11.2 deletion and more severe forms of CHD both contribute to a lower life expectancy than family-based expectations. The results have implications for genetic counseling and anticipatory care. Nature Publishing Group US 2019-04-05 2019 /pmc/articles/PMC6774995/ /pubmed/30948858 http://dx.doi.org/10.1038/s41436-019-0509-y Text en © The Author(s) 2019 Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, and provide a link to the Creative Commons license. You do not have permission under this license to share adapted material derived from this article or parts of it. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-nd/4.0/.
spellingShingle Article
Van, Lily
Heung, Tracy
Graffi, Justin
Ng, Enoch
Malecki, Sarah
Van Mil, Spencer
Boot, Erik
Corral, Maria
Chow, Eva W. C.
Hodgkinson, Kathleen A.
Silversides, Candice
Bassett, Anne S.
All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title_full All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title_fullStr All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title_full_unstemmed All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title_short All-cause mortality and survival in adults with 22q11.2 deletion syndrome
title_sort all-cause mortality and survival in adults with 22q11.2 deletion syndrome
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6774995/
https://www.ncbi.nlm.nih.gov/pubmed/30948858
http://dx.doi.org/10.1038/s41436-019-0509-y
work_keys_str_mv AT vanlily allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT heungtracy allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT graffijustin allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT ngenoch allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT maleckisarah allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT vanmilspencer allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT booterik allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT corralmaria allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT chowevawc allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT hodgkinsonkathleena allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT silversidescandice allcausemortalityandsurvivalinadultswith22q112deletionsyndrome
AT bassettannes allcausemortalityandsurvivalinadultswith22q112deletionsyndrome