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Clinical Implementation and Outcomes of Genetic Testing for Epilepsy by the Ontario Epilepsy Genetic Testing Program

Published online by Cambridge University Press:  14 April 2025

Tugce B. Balci Open the ORCID record for Tugce B. Balci [Opens in a new window] ,
Laila C. Schenkel Open the ORCID record for Laila C. Schenkel [Opens in a new window] ,
Cassandra Rastin ,
Kevin Jones Open the ORCID record for Kevin Jones [Opens in a new window] ,
Lysa Boissé Lomax ,
Jacob Turowec ,
Jennifer Kerkhof ,
Pratibha Bhai ,
Olga Jarinova  and
Stacy Hewson
...Show all authors
Tugce B. Balci
Affiliation:
Division of Genetics, Department of Paediatrics, Western University, London, ON, Canada Medical Genetics Program of Southwestern Ontario, London Health Sciences Centre, London, ON, Canada
Laila C. Schenkel
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
Cassandra Rastin
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada
Kevin Jones
Affiliation:
Division of Pediatric Neurology Department of Pediatrics McMaster University, Hamilton, ON, Canada
Lysa Boissé Lomax
Affiliation:
Division of Neurology Department of Medicine Queen’s University, Kingston, ON, Canada
Jacob Turowec
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada
Jennifer Kerkhof
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada
Pratibha Bhai
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada
Olga Jarinova
Affiliation:
Department of Pathology and Laboratory Medicine, University of Ottawa, Ottawa, ON, Canada Department of Genetics, CHEO, Ottawa, ON, Canada
Stacy Hewson
Affiliation:
Department of Genetic Counselling, The Hospital for Sick Children, Toronto; Department of Molecular Genetics, University of Toronto, Toronto, ON, Canada
A. Narayan Prasad
Affiliation:
Clinical Neurological Sciences, Department of Pediatrics, Western University London, ON, Canada
O. Carter Snead III
Affiliation:
Department of Paediatrics, University of Toronto, Toronto, ON, Canada
David A. Dyment
Affiliation:
Children’s Hospital of Eastern Ontario Research Institute, University of Ottawa, Ottawa, ON, Canada
Bekim Sadikovic*
Affiliation:
Molecular Diagnostics Program and the Verspeeten Clinical Genome Centre, London Health Sciences Centre, London, ON, Canada Department of Pathology and Laboratory Medicine, Western University, London, ON, Canada
*
Corresponding author: Bekim Sadikovic; Email: bekim.sadikovic@lhsc.on.ca
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Abstract:

Background:

Epilepsy is a relatively common condition that affects approximately 4–5 per 1000 individuals in Ontario, Canada. While genetic testing is now prevalent in diagnostic and therapeutic care plans, optimal test selection and interpretation of results in a patient-specific context can be inconsistent and provider dependent.

Methods:

The first of its kind, the Ontario Epilepsy Genetic Testing Program (OEGTP) was launched in 2020 to develop clinical testing criteria, curate gene content, standardize the technical testing criteria through a centralized testing laboratory, assess diagnostic yield and clinical utility and increase genetics literacy among providers.

Results:

Here we present the results of the first two years of the program, demonstrating the overall 20.8% diagnostic yield including pathogenic sequence and copy number variation detected by next-generation sequencing panels. Routine follow-up testing of family members enabled the resolution of ambiguous findings. Post-test outcomes were collected as reported by the ordering clinicians, highlighting the clinical benefits of genetic testing.

Conclusion:

This programmatic approach to genetic testing in epilepsy by OEGTP, together with engagement of clinical and laboratory stakeholders, provided a unique opportunity to gather insight into province-wide implementation of a genetic testing program.

Résumé

RÉSUMÉ

L’Ontario Epilepsy Genetic Testing Program : mise en œuvre clinique du programme et résultats des tests génétiques, relatifs à l’épilepsie

Contexte :

L’épilepsie est une maladie relativement fréquente, qui touche environ 4 – 5 personnes pour 1000, en Ontario, au Canada. Bien que les tests génétiques soient aujourd’hui d’usage courant dans les plans de soins de diagnostic et de traitement, la sélection optimale des tests et l’interprétation des résultats peuvent varier selon les patients et dépendre des fournisseurs de soins.

Méthode :

Premier en son genre en Ontario, le programme Ontario Epilepsy Genetic Testing Program (OEGTP) a été lancé en 2020 afin d’établir des critères de tests cliniques, d’organiser le contenu génétique, d’uniformiser les critères de tests techniques par l’intermédiaire d’un laboratoire central d’analyse, d’évaluer le rendement diagnostique et l’utilité clinique des tests et d’améliorer la compétence informationnelle en génétique chez les fournisseurs de soins.

Résultats :

D’après les résultats ici présentés, obtenus au cours des deux premières années du programme, le rendement diagnostique global est de 20,8 %; il comprend notamment les variations des séquences pathogènes et du nombre de copies détectées par les panels de séquençage de nouvelle génération. Par ailleurs, les tests de suivi courants, effectués parmi les membres des familles touchées, ont permis de résoudre des résultats équivoques. Enfin, les résultats post-tests recueillis comme ils avaient été déclarés par les médecins prescripteurs ont fait ressortir les avantages cliniques des tests génétiques.

Conclusion :

L’approche programmatique des tests génétiques relatifs à l’épilepsie, élaborée dans le cadre de l’OEGTP, en collaboration avec des intervenants cliniques et de laboratoire, a été l’occasion unique de rassembler de l’information sur la mise en œuvre d’un programme de tests génétiques à la grandeur de la province.

Keywords

diagnosticsepilepsynext-generation sequencing
Type
Original Article
Information
Canadian Journal of Neurological Sciences , First View , pp. 1 - 12
Copyright
© The Author(s), 2025. Published by Cambridge University Press on behalf of Canadian Neurological Sciences Federation

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Footnotes

Both Dr Balci and Dr Schenkel had equal contribution as first authors.

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