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Developmental implications of genetic testing for physical indications

European Journal of Human Genetics volume 30, pages 1297–1300 (2022)Cite this article

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Abstract

In children undergoing genetic testing for physical health concerns, we examined how often the results also revealed information about their risk for neurodevelopmental disorders. The study sample consisted of 3056 genetic tests (1686 chromosomal microarrays––CMAs, and 1378 next-generation sequencing––NGS panels) ordered at a tertiary pediatric hospital because of a physical/congenital health problem. Tests ordered to investigate developmental concerns were excluded. Pathogenic, or likely pathogenic variants were manually reviewed for diagnostic likelihood, and for evidence of an association with a neurodevelopmental disorder (e.g., autism or intellectual disability). A total of 169 CMAs (10%) and 232 NGS panels (17%) had likely diagnostic results. More than half (52%) of all diagnostic results had established evidence of a neurodevelopmental disorder association. In summary, there is a high prevalence of neurodevelopmental implications from genetic tests ordered for physical/congenital indications. This broad clinical utility suggests a growing need for genetics-first developmental care pathways.

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Fig. 1: Bar totals show diagnostic yield of individual tests; bars are subdivided by colour to show the proportions with a neurodevelopmental disorder (NDD) association among those with positive results (see Box 1 for criteria).

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Data availability

Data generated and analysed during this study are included in this published article in the supplementary information files; some restrictions have been applied to de-identify variants and protect patient anonymity.

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Acknowledgements

DB acknowledges the Canadian Institutes of Health Research graduate scholarship and the O’Brien scholars program for supporting her fellowship training. SWS holds the Northbridge Chair in Paediatric Research at the Hospital for Sick Children. JV acknowledges the support from the Canadian Institutes of Health Research (PJT-162323).

Author information

Authors and Affiliations

  1. Department of Psychiatry, The Hospital for Sick Children, Toronto, ON, Canada

    Danielle A. Baribeau & Jacob Vorstman

  2. Department of Psychiatry, The University of Toronto, Toronto, ON, Canada

    Danielle A. Baribeau & Jacob Vorstman

  3. Bloorview Research Institute, Holland Bloorview Kids Rehabilitation Hospital, Toronto, ON, Canada

    Danielle A. Baribeau

  4. Department of Genetic Counselling, The Hospital for Sick Children, Toronto, ON, Canada

    Ny Hoang & Thanuja Selvanayagam

  5. Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada

    Ny Hoang, Gregory Costain & Stephen W. Scherer

  6. Genetics and Genome Biology, SickKids Research Institute, Toronto, ON, Canada

    Ny Hoang, Thanuja Selvanayagam, Gregory Costain, Stephen W. Scherer & Jacob Vorstman

  7. Department of Laboratory Medicine & Pathobiology, The Hospital for Sick Children, Toronto, ON, Canada

    D. James Stavropoulos

  8. Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, ON, Canada

    Gregory Costain

  9. The Centre for Applied Genomics, SickKids Research Institute, Toronto, ON, Canada

    Stephen W. Scherer

  10. Autism Research Unit, The Hospital for Sick Children, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Jacob Vorstman

Authors
  1. Danielle A. Baribeau
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  2. Ny Hoang
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  3. Thanuja Selvanayagam
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  4. D. James Stavropoulos
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  6. Stephen W. Scherer
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  7. Jacob Vorstman
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Contributions

DAB and JV and NH conceptualized and designed the study, drafted the initial protocol and manuscript, and revised the manuscript. DJS coordinated and supervised data collection and extraction, supervised the genetic analyses/ variant calls, and critically reviewed the manuscript. GC, DAB and NH conducted the genetic analyses/variant calls and critically reviewed the manuscript. DAB, NH and TS extracted and analyzed the data. SWS, DAB, NH, and TS critically reviewed the manuscript for important intellectual content and scientific rigour. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Corresponding author

Correspondence to Jacob Vorstman.

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Competing interests

JV serves as a consultant for NoBias Therapeutics Inc. SWS is on the scientific advisory committee of Population Bio and is an academic consultant of the King Abdullaziz University. The other authors have no relevant conflicts of interest.

Ethical approval

The study was approved by the institution Research Ethics Boards.

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Baribeau, D.A., Hoang, N., Selvanayagam, T. et al. Developmental implications of genetic testing for physical indications. Eur J Hum Genet 30, 1297–1300 (2022). https://doi.org/10.1038/s41431-022-01181-z

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