The purpose of the study was to implement and prospectively evaluate the outcomes of a rapid genomic diagnosis program at two pediatric tertiary centers.


Rapid singleton whole-exome sequencing (rWES) was performed in acutely unwell pediatric patients with suspected monogenic disorders. Laboratory and clinical barriers to implementation were addressed through continuous multidisciplinary review of process parameters. Diagnostic and clinical utility and cost-effectiveness of rWES were assessed.


Of 40 enrolled patients, 21 (52.5%) received a diagnosis, with median time to report of 16 days (range 9–109 days). A result was provided during the first hospital admission in 28 of 36 inpatients (78%). Clinical management changed in 12 of the 21 diagnosed patients (57%), including the provision of lifesaving treatment, avoidance of invasive biopsies, and palliative care guidance. The cost per diagnosis was AU$13,388 (US$10,453). Additional cost savings from avoidance of planned tests and procedures and reduced length of stay are estimated to be around AU$543,178 (US$424,101). The clear relative advantage of rWES, joint clinical and laboratory leadership, and the creation of a multidisciplinary “rapid team” were key to successful implementation.


Rapid genomic testing in acute pediatrics is not only feasible but also cost-effective, and has high diagnostic and clinical utility. It requires a whole-of-system approach for successful implementation.

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The study was funded by the founding organizations of the Melbourne Genomics Health Alliance and the State Government of Victoria (Department of Health and Human Services). The involvement of the Australian Genome Research Facility was supported by sponsorship from Bioplatforms Australia and the NCRIS program. We thank the patients and families for participating in this study. We are grateful to Ravi Savarirayan, David Amor, Martin Delatycki, Lilian Downie, Emma Krzesinski, Amanda Moody, David Tingay, Kevin Wheeler, Anastasia Pellicano, Leah Hickey, Ruth Armstrong, Trisha Prentice, and Julia Gunn for referring patients to the study; Amber Boys for cytogenetics support; Michael Tamayo and Audrey Chong for sample processing support; Chris Ieng for bioinformatics support; and Hamidul Huque for statistical support.

Author information


  1. Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Australia

    • Zornitza Stark
    • , Sebastian Lunke
    • , Gemma R Brett
    • , Natalie B Tan
    • , Rachel Stapleton
    • , Smitha Kumble
    • , Alison Yeung
    • , Dean G Phelan
    • , Belinda Chong
    • , Miriam Fanjul-Fernandez
    • , Justine E Marum
    • , Anna Jarmolowicz
    • , Jessica R Riseley
    • , Justine Elliott
    • , Tiong Y Tan
    •  & Susan M White
  2. Melbourne Genomics Health Alliance, Melbourne, Australia

    • Zornitza Stark
    • , Gemma R Brett
    • , Alison Yeung
    • , Anna Jarmolowicz
    • , Yael Prawer
    • , Melissa Martyn
    • , Tiong Y Tan
    • , Clara L Gaff
    •  & Susan M White
  3. Department of Paediatrics, University of Melbourne, Melbourne, Australia

    • Zornitza Stark
    • , Miriam Fanjul-Fernandez
    • , Melissa Martyn
    • , Tiong Y Tan
    • , Clara L Gaff
    •  & Susan M White
  4. Monash Genetics, Monash Children’s Hospital, Melbourne, Australia

    • Matthew Hunter
    • , Yael Prawer
    •  & Matthew Regan
  5. Department of Paediatrics, Monash University, Melbourne, Australia

    • Matthew Hunter
  6. Centre for Healthcare Resilience and Implementation Science, Australian Institute of Health Innovation, Macquarie University, Melbourne, Australia

    • Stephanie Best
  7. Department of Medicine, University of Melbourne, Melbourne, Australia

    • Clara L Gaff


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The authors declare no conflict of interest.

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Correspondence to Zornitza Stark.

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