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

Authors

Siddharth Srivastava, Jamie A Love-Nichols, Kira A Dies, David H Ledbetter, Christa L Martin, Wendy K Chung, Helen V Firth, Thomas Frazier, Robin L Hansen, Lisa Prock, Han Brunner, Ny Hoang, Stephen W Scherer, Mustafa Sahin, David T Miller, NDD Exome Scoping Review Work Group

Published in

Genetics in medicine : official journal of the American College of Medical Genetics. Volume 21. Issue 11. Pages 2413-2421. Epub Jun 11, 2019.

Abstract

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.
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.
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%).
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.

PMID:
31182824
Bibliographic data and abstract were imported from PubMed on 10 Dec 2025.

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