Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

Siddharth Srivastava; Jamie A. Love-Nichols; Kira A. Dies; David H. Ledbetter; Christa L. Martin; Wendy K. Chung; Helen Firth; Thomas Frazier; Robin L. Hansen; Lisa Prock; Han Brunner; Ny Hoang; Stephen W. Scherer; Mustafa Sahin; David T. Miller; Bibiana Restrepo; Suma Shankar; Erin Rooney Riggs; Pete Constantinou; Anne Reed-Weston; R. Spencer Tong; Jennifer Howe; Janet Buchanan; Rachel Fisher; Sonal Mahida; NDD Exome Scoping Review Work Group

doi:10.1038/s41436-019-0554-6

Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

Siddharth Srivastava, Jamie A. Love-Nichols, Kira A. Dies, David H. Ledbetter, Christa L. Martin, Wendy K. Chung, Helen Firth, Thomas Frazier, Robin L. Hansen, Lisa Prock, Han Brunner, Ny Hoang, Stephen W. Scherer, Mustafa Sahin^*, David T. Miller, Bibiana Restrepo, Suma Shankar, Erin Rooney Riggs, Pete Constantinou, Anne Reed-WestonR. Spencer Tong, Jennifer Howe, Janet Buchanan, Rachel Fisher, Sonal Mahida, NDD Exome Scoping Review Work Group

^*Corresponding author for this work

Research output: Contribution to journal › (Systematic) Review article › peer-review

195 Citations (Web of Science)

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
Pages (from-to)	2413-2421
Number of pages	9
Journal	Genetics in Medicine
Volume	21
Issue number	11
DOIs	https://doi.org/10.1038/s41436-019-0554-6
Publication status	Published - Nov 2019

Keywords

autism
consensus development conference
diagnostic yield
genetic testing
intellectual disability
AUTISM SPECTRUM DISORDERS
CHROMOSOMAL MICROARRAY
INTELLECTUAL DISABILITY
MEDICAL GENETICS
AMERICAN-COLLEGE
UTILITY
IMPACT
IDENTIFICATION
GUIDELINES
MANAGEMENT

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10.1038/s41436-019-0554-6Licence: CC BY-NC-ND

195 Citations
1 Erratum / corrigendum / retractions

Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders
Srivastava, S., Love-Nichols, J. A., Dies, K. A., Ledbetter, D. H., Martin, C. L., Chung, W. K., Firth, H. V., Frazier, T., Hansen, R. L., Prock, L., Brunner, H., Hoang, N., Scherer, S. W., Sahin, M., Miller, D. T. & NDD Exome Scoping Review Work Group, Oct 2020, In: Genetics in Medicine. 22, 10, p. 1731-1732 2 p.
Research output: Contribution to journal › Erratum / corrigendum / retractions › Academic

Open Access

Cite this

Srivastava, S., Love-Nichols, J. A., Dies, K. A., Ledbetter, D. H., Martin, C. L., Chung, W. K., Firth, H., Frazier, T., Hansen, R. L., Prock, L., Brunner, H., Hoang, N., Scherer, S. W., Sahin, M., Miller, D. T., Restrepo, B., Shankar, S., Riggs, E. R., Constantinou, P., ... NDD Exome Scoping Review Work Group (2019). Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. Genetics in Medicine, 21(11), 2413-2421. https://doi.org/10.1038/s41436-019-0554-6

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title = "Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders",

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.",

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author = "Siddharth Srivastava and Love-Nichols, {Jamie A.} and Dies, {Kira A.} and Ledbetter, {David H.} and Martin, {Christa L.} and Chung, {Wendy K.} and Helen Firth and Thomas Frazier and Hansen, {Robin L.} and Lisa Prock and Han Brunner and Ny Hoang and Scherer, {Stephen W.} and Mustafa Sahin and Miller, {David T.} and Bibiana Restrepo and Suma Shankar and Riggs, {Erin Rooney} and Pete Constantinou and Anne Reed-Weston and Tong, {R. Spencer} and Jennifer Howe and Janet Buchanan and Rachel Fisher and Sonal Mahida and {NDD Exome Scoping Review Work Group}",

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Srivastava, S, Love-Nichols, JA, Dies, KA, Ledbetter, DH, Martin, CL, Chung, WK, Firth, H, Frazier, T, Hansen, RL, Prock, L, Brunner, H, Hoang, N, Scherer, SW, Sahin, M, Miller, DT, Restrepo, B, Shankar, S, Riggs, ER, Constantinou, P, Reed-Weston, A, Tong, RS, Howe, J, Buchanan, J, Fisher, R, Mahida, S & NDD Exome Scoping Review Work Group 2019, 'Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders', Genetics in Medicine, vol. 21, no. 11, pp. 2413-2421. https://doi.org/10.1038/s41436-019-0554-6

Meta-analysis and multidisciplinary consensus statement : exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders. / Srivastava, Siddharth; Love-Nichols, Jamie A.; Dies, Kira A. et al.

In: Genetics in Medicine, Vol. 21, No. 11, 11.2019, p. 2413-2421.

Research output: Contribution to journal › (Systematic) Review article › peer-review

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 - 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

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.

AU - Restrepo, Bibiana

AU - Shankar, Suma

AU - Riggs, Erin Rooney

AU - Constantinou, Pete

AU - Reed-Weston, Anne

AU - Tong, R. Spencer

AU - Howe, Jennifer

AU - Buchanan, Janet

AU - Fisher, Rachel

AU - Mahida, Sonal

AU - NDD Exome Scoping Review Work Group

PY - 2019/11

Y1 - 2019/11

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

KW - AUTISM SPECTRUM DISORDERS

KW - CHROMOSOMAL MICROARRAY

KW - INTELLECTUAL DISABILITY

KW - MEDICAL GENETICS

KW - AMERICAN-COLLEGE

KW - UTILITY

KW - IMPACT

KW - IDENTIFICATION

KW - GUIDELINES

KW - MANAGEMENT

U2 - 10.1038/s41436-019-0554-6

DO - 10.1038/s41436-019-0554-6

M3 - (Systematic) Review article

VL - 21

SP - 2413

EP - 2421

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 11

ER -

Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

Abstract

Keywords

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Research output

Correction: Meta-analysis and multidisciplinary consensus statement: exome sequencing is a first-tier clinical diagnostic test for individuals with neurodevelopmental disorders

Cite this