Clinical Application of Genome and Exome Sequencing as a Diagnostic Tool for Pediatric Patients: a Scoping Review of the Literature

Genet Med. 2019 Jan;21(1):3-16. doi: 10.1038/s41436-018-0024-6. Epub 2018 May 14.


Purpose: Availability of clinical genomic sequencing (CGS) has generated questions about the value of genome and exome sequencing as a diagnostic tool. Analysis of reported CGS application can inform uptake and direct further research. This scoping literature review aims to synthesize evidence on the clinical and economic impact of CGS.

Methods: PubMed, Embase, and Cochrane were searched for peer-reviewed articles published between 2009 and 2017 on diagnostic CGS for infant and pediatric patients. Articles were classified according to sample size and whether economic evaluation was a primary research objective. Data on patient characteristics, clinical setting, and outcomes were extracted and narratively synthesized.

Results: Of 171 included articles, 131 were case reports, 40 were aggregate analyses, and 4 had a primary economic evaluation aim. Diagnostic yield was the only consistently reported outcome. Median diagnostic yield in aggregate analyses was 33.2% but varied by broad clinical categories and test type.

Conclusion: Reported CGS use has rapidly increased and spans diverse clinical settings and patient phenotypes. Economic evaluations support the cost-saving potential of diagnostic CGS. Multidisciplinary implementation research, including more robust outcome measurement and economic evaluation, is needed to demonstrate clinical utility and cost-effectiveness of CGS.

Keywords: Clinical implementation; Medical genomics; Review; exome sequencing; genome sequencing.

Publication types

  • Review

MeSH terms

  • Cost-Benefit Analysis
  • Exome / genetics
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics*
  • Genome, Human / genetics*
  • Humans
  • Pediatrics / trends
  • Whole Exome Sequencing / economics
  • Whole Exome Sequencing / trends*
  • Whole Genome Sequencing / economics
  • Whole Genome Sequencing / trends*