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Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)
  1. Melissa T Carter1,
  2. Myriam Srour2,3,
  3. Ping-Yee Billie Au4,
  4. Daniela Buhas5,6,
  5. Sarah Dyack7,8,
  6. Alison Eaton9,10,
  7. Michal Inbar-Feigenberg11,
  8. Heather Howley12,
  9. Anne Kawamura13,14,15,16,
  10. Suzanne M E Lewis17,
  11. Elizabeth McCready18,19,
  12. Tanya N Nelson20,
  13. Hilary Vallance20
  14. on behalf of the Canadian College of Medical Geneticists
  1. 1 Department of Genetics, CHEO, Ottawa, Ontario, Canada
  2. 2 Division of Neurology, McGill University Health Centre, Montreal, Québec, Canada
  3. 3 Department of Pediatrics, McGill University, Montréal, QC, Canada
  4. 4 Department of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta, Canada
  5. 5 Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, McGill University, Montreal, Québec, Canada
  6. 6 Department of Human Genetics, McGill University, Montreal, QC, Canada
  7. 7 Division of Medical Genetics, IWK Health Centre, Halifax, Nova Scotia, Canada
  8. 8 Department of Pediatrics, Dalhousie University, Halifax, NS, Canada
  9. 9 Department of Medical Genetics, Stollery Children's Hospital, Edmonton, Alberta, Canada
  10. 10 Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada
  11. 11 Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada
  12. 12 Office of Research Services, CHEO Research Institute, Ottawa, Ontario, Canada
  13. 13 Division of Developmental Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada
  14. 14 Department of Paediatrics, University of Toronto, Toronto, ON, Canada
  15. 15 Mental Health and Developmental Disability Committee, Canadian Pediatric Society, Ottawa, ON, Canada
  16. 16 Canadian Paediatric Society, Toronto, Ontario, Canada
  17. 17 Department of Medical Genetics, BC Children's and Women's Hospital, Vancouver, British Columbia, Canada
  18. 18 Department of Pathology and Molecular Medicine, McMaster University, McMaster University, Hamilton, ON, Canada, Hamilton, Ontario, Canada
  19. 19 Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences Centre, Hamilton, ON, Canada
  20. 20 Department of Pathology and Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada
  1. Correspondence to Melissa T Carter, Genetics, Children's Hospital of Eastern Ontario, Ottawa, ON K1H 8L1, Canada; mcarter{at}


Purpose and scope The aim of this position statement is to provide recommendations for clinicians regarding the use of genetic and metabolic investigations for patients with neurodevelopmental disorders (NDDs), specifically, patients with global developmental delay (GDD), intellectual disability (ID) and/or autism spectrum disorder (ASD). This document also provides guidance for primary care and non-genetics specialists caring for these patients while awaiting consultation with a clinical geneticist or metabolic specialist.

Methods of statement development A multidisciplinary group reviewed existing literature and guidelines on the use of genetic and metabolic investigations for the diagnosis of NDDs and synthesised the evidence to make recommendations relevant to the Canadian context. The statement was circulated for comment to the Canadian College of Medical Geneticists (CCMG) membership-at-large and to the Canadian Pediatric Society (Mental Health and Developmental Disabilities Committee); following incorporation of feedback, it was approved by the CCMG Board of Directors on 1 September 2022.

Results and conclusions Chromosomal microarray is recommended as a first-tier test for patients with GDD, ID or ASD. Fragile X testing should also be done as a first-tier test when there are suggestive clinical features or family history. Metabolic investigations should be done if there are clinical features suggestive of an inherited metabolic disease, while the patient awaits consultation with a metabolic physician. Exome sequencing or a comprehensive gene panel is recommended as a second-tier test for patients with GDD or ID. Genetic testing is not recommended for patients with NDDs in the absence of GDD, ID or ASD, unless accompanied by clinical features suggestive of a syndromic aetiology or inherited metabolic disease.

  • genetics, medical
  • clinical decision-making
  • genetics
  • genetic testing

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See:

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  • Correction notice This article has been corrected since it was published online first. The placement of tables 2 and 3 has been corrected within the article.

  • Contributors MTC, MS and HV were responsible for identifying the literature, summarising subgroup meetings and drafting their test-specific sections. MTC, HV and HH were responsible for drafting the manuscript. All authors contributed to literature review, the conception and design of the position statement, interpretation of data, writing and critical revisions contributing to the intellectual content and approval of the final version of the manuscript.

  • Funding HH was supported with funding from the Canadian College of Medical Geneticists. SMEL is supported by an Investigator Grant Award through BC Children’s Hospital Research Institute.

  • Competing interests TNN: spouse employed by Illumina.

  • Provenance and peer review Not commissioned; externally peer reviewed.