Integrating exome sequencing into a diagnostic pathway for epileptic encephalopathy: Evidence of clinical utility and cost effectiveness

Elizabeth E. Palmer, Deborah Schofield, Rupendra Shrestha, Tejaswi Kandula, Rebecca Macintosh, John A. Lawson, Ian Andrews, Hugo Sampaio, Alexandra M. Johnson , Michelle A. Farrar, Michael Cardamone, David Mowat, George Elakis, William Lo, Ying Zhu, Kevin Ying, Paula Morris, Jiang Tao, Kerith-Rae Dias, Michael BuckleyMarcel E. Dinger, Mark J. Cowley, Tony Roscioli, Edwin P. Kirk, Ann Bye, Rani K. Sachdev

Research output: Contribution to journalArticlepeer-review

28 Citations (Scopus)
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Background: Epileptic encephalopathies are a devastating group of neurological conditions in which etiological diagnosis can alter management and clinical outcome. Exome sequencing and gene panel testing can improve diagnostic yield but there is no cost‐effectiveness analysis of their use or consensus on how to best integrate these tests into clinical diagnostic pathways.

Methods: We conducted a retrospective cost‐effectiveness study comparing trio exome sequencing with a standard diagnostic approach, for a well‐phenotyped cohort of 32 patients with epileptic encephalopathy, who remained undiagnosed after “first‐tier” testing. Sensitivity analysis was included with a range of commercial exome and multigene panels.

Results: The diagnostic yield was higher for the exome sequencing (16/32; 50%) than the standard arm (2/32; 6.2%). The trio exome sequencing pathway was cost‐effective compared to the standard diagnostic pathway with a cost saving of AU$5,236 (95% confidence intervals $2,482; $9,784) per additional diagnosis; the standard pathway cost approximately 10 times more per diagnosis. Sensitivity analysis demonstrated that the majority of commercial exome sequencing and multigene panels studied were also cost‐effective. The clinical utility of all diagnoses was reported.

Conclusion: Our study supports the integration of exome sequencing and gene panel testing into the diagnostic pathway for epileptic encephalopathy, both in terms of cost effectiveness and clinical utility. We propose a diagnostic pathway that integrates initial rapid screening for treatable causes and comprehensive genomic screening. This study has important implications for health policy and public funding for epileptic encephalopathy and other neurological conditions.
Original languageEnglish
Pages (from-to)186-199
Number of pages14
JournalMolecular Genetics and Genomic Medicine
Issue number2
Publication statusPublished - Mar 2018
Externally publishedYes

Bibliographical note

Copyright 2017 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals, Inc. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.


  • diagnosis
  • epilepsy
  • genomics
  • health economics

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