A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

Lisenka E. L. M. Vissers; Kirsten J. M. van Nimwegen; Jolanda H. Schieving; Erik-Jan Kamsteeg; Tjitske Kleefstra; Helger G. Yntema; Rolph Pfundt; Gert Jan van der Wilt; Lotte Krabbenborg; Han G. Brunner; Simone van der Burg; Janneke Grutters; Joris A. Veltman; Michel A. A. P. Willemsen

doi:10.1038/gim.2017.1

A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

Lisenka E. L. M. Vissers^*, Kirsten J. M. van Nimwegen, Jolanda H. Schieving, Erik-Jan Kamsteeg, Tjitske Kleefstra, Helger G. Yntema, Rolph Pfundt, Gert Jan van der Wilt, Lotte Krabbenborg, Han G. Brunner, Simone van der Burg, Janneke Grutters, Joris A. Veltman, Michel A. A. P. Willemsen

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

Abstract

Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.

Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously.

Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.

Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.

Original language	English
Pages (from-to)	1055-1063
Number of pages	9
Journal	Genetics in Medicine
Volume	19
Issue number	9
DOIs	https://doi.org/10.1038/gim.2017.1
Publication status	Published - Sept 2017

Keywords

diagnostic yield
health-care resource use
Prospective Clinical Utility Study
pediatric neurology
whole-exome sequencing
INCIDENTAL FINDINGS
INTELLECTUAL DISABILITY
RARE DISEASES
MUTATIONS
COST
PARTICIPANTS
DISORDERS
DIAGNOSIS
CONSENSUS
VARIANTS

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Cite this

Vissers, L. E. L. M., van Nimwegen, K. J. M., Schieving, J. H., Kamsteeg, E.-J., Kleefstra, T., Yntema, H. G., Pfundt, R., van der Wilt, G. J., Krabbenborg, L., Brunner, H. G., van der Burg, S., Grutters, J., Veltman, J. A., & Willemsen, M. A. A. P. (2017). A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology. Genetics in Medicine, 19(9), 1055-1063. https://doi.org/10.1038/gim.2017.1

@article{6709d836c25f401d85886965e7d3a13b,

title = "A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology",

abstract = "Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously.Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.",

keywords = "diagnostic yield, health-care resource use, Prospective Clinical Utility Study, pediatric neurology, whole-exome sequencing, INCIDENTAL FINDINGS, INTELLECTUAL DISABILITY, RARE DISEASES, MUTATIONS, COST, PARTICIPANTS, DISORDERS, DIAGNOSIS, CONSENSUS, VARIANTS",

author = "Vissers, {Lisenka E. L. M.} and {van Nimwegen}, {Kirsten J. M.} and Schieving, {Jolanda H.} and Erik-Jan Kamsteeg and Tjitske Kleefstra and Yntema, {Helger G.} and Rolph Pfundt and {van der Wilt}, {Gert Jan} and Lotte Krabbenborg and Brunner, {Han G.} and {van der Burg}, Simone and Janneke Grutters and Veltman, {Joris A.} and Willemsen, {Michel A. A. P.}",

year = "2017",

month = sep,

doi = "10.1038/gim.2017.1",

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Vissers, LELM, van Nimwegen, KJM, Schieving, JH, Kamsteeg, E-J, Kleefstra, T, Yntema, HG, Pfundt, R, van der Wilt, GJ, Krabbenborg, L, Brunner, HG, van der Burg, S, Grutters, J, Veltman, JA & Willemsen, MAAP 2017, 'A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology', Genetics in Medicine, vol. 19, no. 9, pp. 1055-1063. https://doi.org/10.1038/gim.2017.1

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T1 - A clinical utility study of exome sequencing versus conventional genetic testing in pediatric neurology

AU - Vissers, Lisenka E. L. M.

AU - van Nimwegen, Kirsten J. M.

AU - Schieving, Jolanda H.

AU - Kamsteeg, Erik-Jan

AU - Kleefstra, Tjitske

AU - Yntema, Helger G.

AU - Pfundt, Rolph

AU - van der Wilt, Gert Jan

AU - Krabbenborg, Lotte

AU - Brunner, Han G.

AU - van der Burg, Simone

AU - Grutters, Janneke

AU - Veltman, Joris A.

AU - Willemsen, Michel A. A. P.

PY - 2017/9

Y1 - 2017/9

N2 - Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously.Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.

AB - Purpose: Implementation of novel genetic diagnostic tests is generally driven by technological advances because they promise shorter turnaround times and/or higher diagnostic yields. Other aspects, including impact on clinical management or cost-effectiveness, are often not assessed in detail prior to implementation.Methods: We studied the clinical utility of whole-exome sequencing (WES) in complex pediatric neurology in terms of diagnostic yield and costs. We analyzed 150 patients (and their parents) presenting with complex neurological disorders of suspected genetic origin. In a parallel study, all patients received both the standard diagnostic workup (e.g., cerebral imaging, muscle biopsies or lumbar punctures, and sequential gene-by-gene-based testing) and WES simultaneously.Results: Our unique study design allowed direct comparison of diagnostic yield of both trajectories and provided insight into the economic implications of implementing WES in this diagnostic trajectory. We showed that WES identified significantly more conclusive diagnoses (29.3%) than the standard care pathway (7.3%) without incurring higher costs. Exploratory analysis of WES as a first-tier diagnostic test indicates that WES may even be cost-saving, depending on the extent of other tests being omitted.Conclusion: Our data support such a use of WES in pediatric neurology for disorders of presumed genetic origin.

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KW - INCIDENTAL FINDINGS

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KW - RARE DISEASES

KW - MUTATIONS

KW - COST

KW - PARTICIPANTS

KW - DISORDERS

KW - DIAGNOSIS

KW - CONSENSUS

KW - VARIANTS

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