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Epilepsy Genetics

Epilepsy is a clinically heterogeneous disease with diverse aetiologies. Advances in molecular genetics over the last ten years have led to an explosion of novel genes implicated in monogenic and complex genetic epilepsies. Therefore, genetic testing now has become a critical part of the diagnostic evaluation of adults and children with epilepsy to identify genetic epilepsy syndromes, guide treatment, optimize genetic counseling, and bring closure and peace of mind to the families of those with a genetic disease whether treatable or not.


The Ontario Epilepsy Genetic Testing Program [OEGTP]

On October 1, 2020, the Ontario Ministry Health [MOH] established epilepsy gene panel testing in Ontario as a publicly funded service for patient's who meet the ministry's eligibility criteria. Therefore, after this date, the MOH's Out-of-Country/Out-of-Province (OOC/OOP) Prior Approval Program for Laboratory Testing will no longer be accepting applications for epilepsy panel testing and ordering physicians will be redirected to the testing provided in Ontario.

Specifically, based on the recommendations of an MOH epilepsy genetics advisory group, the Ontario Epilepsy Genetics Testing Program [OEGTP] will provide evidence-based epilepsy gene panels ID:31587668 for properly selected epilepsy patients. This genetic testing will be carried out at the Division of Molecular Diagnostics in the Pathology and Laboratory Medicine Department at London Health Sciences Centre www.lhsc.on.ca/palm/labs/molecular.

Access to epilepsy genetic testing now is available through a new requisition that is designed to provide information critical to interpretation of the genetic test results and genetics counseling OEGTP Requisition. As well, the health care provider who orders the genetic epilepsy test and receives the result will be required to complete the OEGTP Management impact form www.lhsc.on.ca/palm/labs/molecular, which will provide data concerning the impact of results of epilepsy genetic testing using multigene panels on patient management. These management impact data are critical to ongoing evidence-based analysis and clinical oversight of the OEGTP with resultant expert guidance used for continuously improving the service for better patient care and impact going forward.

Project ECHO Epilepsy Across the Life Span and the OEGTP

With the advent of OGETP Epileptologists and Neurologists affiliated with Ontario District and Regional Epilepsy Centres, FRCP Neurologists with a minimum of six months of training in epilepsy and EEG, and Geneticists can order genetic testing in epilepsy patients. In addition, Ontario licensed physicians who acknowledge completion of the Continuing Medical Education (CME) certified epilepsy genetics curriculum in Project ECHO Epilepsy Across the Life Span will be able to order genetic testing for their epilepsy patients, where indicated,through the OEGTP. Project ECHO Epilepsy Across the Lifespan is a provider education opportunity targeted at Family Physicians, Paediatricians and Community Neurologists.

Project ECHO (Extension for Community Healthcare Outcomes) is an innovative model for medical education that uses video-conferencing with case-based learning to connect specialist multidisciplinary teams at academic health centres to community healthcare providers. In this way Project ECHO: Epilepsy Across the Lifespan delivers pediatric and adult epilepsy curricula to improve the quality and accessibility of epilepsy care in Ontario. ECHO ONTARIOThe genetics of epilepsy now is an integral part of the Project ECHO Epilepsy Across the Life Span curricula. This epilepsy genetics curricula may be found below and will be provided in our next ECHO cycle in February 2021.

This one-credit-per-hour Group Learning program meets the certification criteria of the College of Family Physicians of Canada and has been certified by Continuing Professional Development, Faculty of Medicine, University of Toronto for Mainpro+ credits. These sessions are also an Accredited Group Learning Activity (Section 1) as defined by the Maintenance of Certification Program of the Royal College of Physicians and Surgeons of Canada, approved by Continuing Professional Development, Faculty of Medicine, University of Toronto.


OEGTP - EPILEPSY TEST PANELS

Comprehensive Epilepsy panel: 167 Genes

ACTB, ACTG1, ADSL, AKT3, ALDH7A1, AMT, AP3B2, ARFGEF2, ARHGEF9, ARV1, ARX, ASAH1, ASNS, ATP1A3, ATP6V0A2, ATP7A, ATRX, B3GALNT2, B3GNT1(B4GAT1), CACNA1A, CAD, CDKL5, CHD2, CHRNA2, CHRNA4, CHRNB2, CLN3, CLN5, CLN6, CLN8, CNTNAP2, CPA6, CSTB, CTSD, DCX, DENND5A, DEPDC5, DNAJC5, DNM1, DOCK7, DYNC1H1, DYRK1A, EEF1A2, EHMT1, EPM2A, FGF12, FKRP, FKTN, FLNA, FOLR1, FOXG1, FRRS1L, GABRA1, GABRB3, GABRG2, GAMT, GLDC, GMPPB, GNAO1, GOSR2, GPR56 (ADGRG1), GPSM2, GRIN2A, GRIN2B, GTDC2(POMGNT2), HCN1, HNRNPU, ITPA, KANSL1, KATNB1, KCNA2, KCNB1, KCNC1, KCNJ10, KCNMA1, KCNQ2, KCNQ3, KCNT1, KCTD7(CLN14), KDM5C, KIAA1279(KIF1BP), KIF2A, LAMA2, LARGE, LGI1, LMNB2, MBD5, MDH2, MECP2, MEF2C, MFSD8, MOCS1, NDE1, NEU1, NHLRC1, NPRL2, NPRL3, NRXN1, OCLN, PAFAH1B1, PAK3, PCDH19, PHF6, PHGDH, PIGA, PLCB1, PNKP, PNPO, POLG, POMGNT1, POMT1, POMT2, PPT1, PRICKLE1, PROSC(PLPBP), PRRT2, PSAT1, PSPH, RAB18, RAB39B, RAB3GAP1, RAB3GAP2, RELN, ROGDI, RTTN, SCARB2, SCN1A, SCN1B, SCN2A, SCN8A, SGCE, SGK196(POMK), SLC12A5, SLC13A5, SLC25A12, SLC25A22, SLC2A1, SLC35A2, SLC6A8, SLC9A6, SNAP29, SPTAN1, SRD5A3, STX1B, STXBP1, SUOX, SYN1, SYNGAP1, SYNJ1, SZT2, TBC1D24, TCF4, TPP1, TSC1, TSC2, TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, UBA5, UBE3A, VLDLR, WDR62, WWOX, YWHAG, ZEB2

Focal Epilepsy panel: 14 Genes

CHRNA2, CHRNA4, CHRNB2, CPA6, DEPDC5, GRIN2A, KCNT1, LGI1, NPRL2, NPRL3, PRRT2, SCN1A, SCN1B, SLC2A1

Progressive Myoclonic Epilepsy panel: 20 Genes

ASAH1, CLN3, CLN5, CLN6, CLN8, CSTB, CTSD, EPM2A, GOSR2, KCNC1, KCTD7(CLN14), LMNB2, MFSD8, NEU1, NHLRC1, PPT1, PRICKLE1, SCARB2, SGCE, TPP1

Early Infantile Epilepsy panel: 51 Genes

AP3B2, ARHGEF9, ARV1, ARX, CACNA1A, CAD, CDKL5, CHD2, DENND5A, DNM1, DOCK7, EEF1A2, FGF12, FRRS1L, GABRA1, GABRB3, GNAO1, GRIN2A, GRIN2B, HCN1, HNRNPU, ITPA, KCNA2, KCNB1, KCNQ2, KCNT1, MDH2, MECP2, MEF2C, PCDH19, PIGA, PLCB1, PNKP, PRRT2, SCN1A, SCN2A, SCN8A, SLC12A5, SLC13A5, SLC25A12, SLC25A22, SLC35A2, SPTAN1, STXBP1, SYNGAP1, SYNJ1, SZT2, TBC1D24, UBA5, WWOX, YWHAG

Childhood Onset Epilepsy panel: 45 Genes

ADSL, ARX, ATP1A3, ATRX, CDKL5, CHD2, CNTNAP2, DEPDC5, DNAJC5, DYRK1A, EHMT1, FOXG1, GABRG2, GRIN2A, KANSL1, KCNJ10, KCNMA1, KCNQ3, KDM5C, MBD5, MECP2, MEF2C, NRXN1, PAK3, PCDH19, PHF6, PIGA, PNKP, PRRT2, RAB39B, ROGDI, SCN1A, SCN1B, SCN2A, SLC2A1, SLC9A6, STX1B, SYN1, SYNGAP1, TBC1D24, TCF4, TSC1, TSC2, UBE3A, ZEB2

Brain Malformation Epilepsy panel: 44 Genes

ACTB, ACTG1, AKT3, ARFGEF2, ARX, ASNS, ATP6V0A2, B3GALNT2, B3GNT1(B4GAT1), DCX, DYNC1H1, FKRP, FKTN, FLNA, GMPPB, GPR56(ADGRG1), GPSM2, GTDC2(POMGNT2), KATNB1, KIAA1279(KIF1BP), KIF2A, LAMA2, LARGE, NDE1, OCLN, PAFAH1B1, POMGNT1, POMT1, POMT2, RAB18, RAB3GAP1, RAB3GAP2, RELN, RTTN, SGK196(POMK), SNAP29, SRD5A3, TUBA1A, TUBB, TUBB2A, TUBB2B, TUBB3, VLDLR, WDR62

Actionable Gene Epilepsy panel: 22 Genes

ALDH7A1, AMT, ATP7A, CAD, FOLR1, GAMT, GLDC, KCNQ2, KCNT1, MOCS1, PHGDH, PNPO, POLG, PROSC(PLPBP), PSAT1, PSPH, SCNA1, SLC2A1, SLC6A8, SUOX, TSC1, TSC2

TEST INDICATIONS

This Epilepsy panel test is a deep sequencing NGS assay designed as a rule out sequencing and copy number analysis test for all coding sequences of all genes tested. Content is designed by a panel of clinical experts Ontario MOHLTC Genetic Epilepsy Working Group to include majority of genes associated with epilepsy as the cardinal clinical presentation. In patients where epilepsy is not the cardinal clinical feature, and genetic etiology is suspected, other genetic and genomic analyses and clinical genetics referral may be considered.

Physicians must include completed questionnaire prior to submitting specimens to PaLM and confirm that age of onset, seizure type and electroclinical syndrome is consistent with a genetic epilepsy. Ontario Epilepsy Genetics Testing Program Requistion

OEGTP Requisition for Print

OEGTP Post Test Questionnaire

OEGTP Algorithm

Schulich School of Medicine and Dentistry London Health Sciences CentreSt. Joseph's Health Care LondonWestern University