Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)

Melissa T Carter; Myriam Srour; Ping-Yee Billie Au; Daniela Buhas; Sarah Dyack; Alison Eaton; Michal Inbar-Feigenberg; Heather Howley; Anne Kawamura; Suzanne M E Lewis; Elizabeth McCready; Tanya N Nelson; Hilary Vallance; Canadian College of Medical Geneticists

doi:10.1136/jmg-2022-108962

Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)

J Med Genet. 2023 Jun;60(6):523-532. doi: 10.1136/jmg-2022-108962. Epub 2023 Feb 23.

Authors

Melissa T Carter¹, Myriam Srour^{2

3}, Ping-Yee Billie Au⁴, Daniela Buhas^{5

6}, Sarah Dyack^{7

8}, Alison Eaton^{9

10}, Michal Inbar-Feigenberg¹¹, Heather Howley¹², Anne Kawamura^{13

14

15

16}, Suzanne M E Lewis¹⁷, Elizabeth McCready^{18

19}, Tanya N Nelson²⁰, Hilary Vallance²⁰; Canadian College of Medical Geneticists

Affiliations

¹ Department of Genetics, CHEO, Ottawa, Ontario, Canada mcarter@cheo.on.ca.
² Division of Neurology, McGill University Health Centre, Montreal, Québec, Canada.
³ Department of Pediatrics, McGill University, Montréal, QC, Canada.
⁴ Department of Medical Genetics, Alberta Children's Hospital, Calgary, Alberta, Canada.
⁵ Division of Medical Genetics, Department of Specialized Medicine, McGill University Health Centre, McGill University, Montreal, Québec, Canada.
⁶ Department of Human Genetics, McGill University, Montreal, QC, Canada.
⁷ Division of Medical Genetics, IWK Health Centre, Halifax, Nova Scotia, Canada.
⁸ Department of Pediatrics, Dalhousie University, Halifax, NS, Canada.
⁹ Department of Medical Genetics, Stollery Children's Hospital, Edmonton, Alberta, Canada.
¹⁰ Department of Medical Genetics, University of Alberta, Edmonton, AB, Canada.
¹¹ Division of Clinical and Metabolic Genetics, The Hospital for Sick Children, Toronto, Ontario, Canada.
¹² Office of Research Services, CHEO Research Institute, Ottawa, Ontario, Canada.
¹³ Division of Developmental Pediatrics, Holland Bloorview Kids Rehabilitation Hospital, Toronto, Ontario, Canada.
¹⁴ Department of Paediatrics, University of Toronto, Toronto, ON, Canada.
¹⁵ Mental Health and Developmental Disability Committee, Canadian Pediatric Society, Ottawa, ON, Canada.
¹⁶ Canadian Paediatric Society, Toronto, Ontario, Canada.
¹⁷ Department of Medical Genetics, BC Children's and Women's Hospital, Vancouver, British Columbia, Canada.
¹⁸ Department of Pathology and Molecular Medicine, McMaster University, McMaster University, Hamilton, ON, Canada, Hamilton, Ontario, Canada.
¹⁹ Hamilton Regional Laboratory Medicine Program, Hamilton Health Sciences Centre, Hamilton, ON, Canada.
²⁰ Department of Pathology and Laboratory Medicine, BC Children's Hospital, University of British Columbia, Vancouver, British Columbia, Canada.

Abstract

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.

Keywords: clinical decision-making; genetic testing; genetics; genetics, medical.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Autism Spectrum Disorder* / diagnosis
Autism Spectrum Disorder* / genetics
Canada
Child
Genetic Testing / methods
Humans
Intellectual Disability* / diagnosis
Intellectual Disability* / genetics
Neurodevelopmental Disorders* / diagnosis
Neurodevelopmental Disorders* / genetics
Physicians*