Abstract
Purpose: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. Methods: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. Results: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15–20%). Conclusion: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.
| Original language | English (US) |
|---|---|
| Journal | Genetics in Medicine |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- autism
- consensus development conference
- diagnostic yield
- genetic testing
- intellectual disability
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
Meta-analysis and multidisciplinary consensus statement : exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. / the NDD Exome Scoping Review Work Group.
In: Genetics in Medicine, 01.01.2019.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Meta-analysis and multidisciplinary consensus statement
T2 - exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders
AU - the NDD Exome Scoping Review Work Group
AU - Srivastava, Siddharth
AU - Love-Nichols, Jamie A.
AU - Dies, Kira A.
AU - Ledbetter, David H.
AU - Martin, Christa L.
AU - Chung, Wendy K.
AU - Firth, Helen V.
AU - Frazier, Thomas
AU - Hansen, Robin L
AU - Prock, Lisa
AU - Brunner, Han
AU - Hoang, Ny
AU - Scherer, Stephen W.
AU - Sahin, Mustafa
AU - Miller, David T.
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Purpose: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. Methods: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. Results: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15–20%). Conclusion: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.
AB - Purpose: For neurodevelopmental disorders (NDDs), etiological evaluation can be a diagnostic odyssey involving numerous genetic tests, underscoring the need to develop a streamlined algorithm maximizing molecular diagnostic yield for this clinical indication. Our objective was to compare the yield of exome sequencing (ES) with that of chromosomal microarray (CMA), the current first-tier test for NDDs. Methods: We performed a PubMed scoping review and meta-analysis investigating the diagnostic yield of ES for NDDs as the basis of a consensus development conference. We defined NDD as global developmental delay, intellectual disability, and/or autism spectrum disorder. The consensus development conference included input from genetics professionals, pediatric neurologists, and developmental behavioral pediatricians. Results: After applying strict inclusion/exclusion criteria, we identified 30 articles with data on molecular diagnostic yield in individuals with isolated NDD, or NDD plus associated conditions (such as Rett-like features). Yield of ES was 36% overall, 31% for isolated NDD, and 53% for the NDD plus associated conditions. ES yield for NDDs is markedly greater than previous studies of CMA (15–20%). Conclusion: Our review demonstrates that ES consistently outperforms CMA for evaluation of unexplained NDDs. We propose a diagnostic algorithm placing ES at the beginning of the evaluation of unexplained NDDs.
KW - autism
KW - consensus development conference
KW - diagnostic yield
KW - genetic testing
KW - intellectual disability
UR - http://www.scopus.com/inward/record.url?scp=85067249960&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85067249960&partnerID=8YFLogxK
U2 - 10.1038/s41436-019-0554-6
DO - 10.1038/s41436-019-0554-6
M3 - Article
C2 - 31182824
AN - SCOPUS:85067249960
JO - Genetics in Medicine
JF - Genetics in Medicine
SN - 1098-3600
ER -