Pulse Brain · Growing Health Evidence Index
Tier 1 — Meta-analysis / systematic reviewPeer-reviewedConventional

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

Siddharth Srivastava, Jamie Love‐Nichols, Kira A. Dies, David H. Ledbetter, Christa Lese Martin, Wendy K. Chung, Helen V. Firth, Thomas Frazier, Robin Hansen, Lisa M. Prock, Han G. Brunner, Ny Hoang, Stephen W. Scherer, Mustafa Şahin, David T. Miller

Genetics in Medicine · 2019

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Summary

This meta-analysis and consensus statement evaluated the diagnostic performance of exome sequencing versus chromosomal microarray for individuals with neurodevelopmental disorders (global developmental delay, intellectual disability, autism spectrum disorder). The authors identified 30 studies and found ES yield substantially exceeded CMA (36% overall versus 15-20%), leading to a consensus recommendation placing ES as a first-tier diagnostic test rather than a downstream investigation.

Regional applicability

This is an international consensus statement with no specific geographic restriction. The findings are applicable to United Kingdom clinical genetics services and paediatric neurology practice, as NHS diagnostic algorithms for NDDs would benefit from evidence-based tier ordering. However, implementation depends on UK-specific service capacity, funding, and NICE guidance adoption.

Key measures

Molecular diagnostic yield (percentage of individuals with identified genetic diagnosis); stratified by NDD type (isolated versus NDD plus associated conditions)

Outcomes reported

The study compared diagnostic yield of exome sequencing (ES) versus chromosomal microarray (CMA) for neurodevelopmental disorders through meta-analysis of 30 peer-reviewed articles. Overall ES yield was 36% (31% for isolated NDD, 53% for NDD with associated conditions) versus 15-20% for CMA.

Theme
General food systems / other
Subject
Other / interdisciplinary
Study type
Meta-analysis
Study design
Meta-analysis
Source type
Peer-reviewed study
Status
Published
Geography
International
System type
Human clinical
DOI
10.1038/s41436-019-0554-6
Catalogue ID
SNmp7umala-ye6h4b

Topic tags

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