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Genetic testing in children enrolled in epilepsy surgery program. A real-life study

B. Straka, B. Splitkova, M. Vlckova, P. Tesner, H. Rezacova, L. Krskova, M. Koblizek, M. Kyncl, A. Maulisova, K. Bukacova, A. Uhrova-Meszarosova, A. Musilova, M. Kudr, M. Ebel, A. Belohlavkova, A. Jahodova, P. Liby, M. Tichy, P. Jezdik, J....

. 2023 ; 47 (-) : 80-87. [pub] 20231005

Language English Country England, Great Britain

Document type Journal Article

Persistent link   https://www.medvik.cz/link/bmc24000813

OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.

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$a Straka, Barbora $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: barbora.straka@fnmotol.cz $7 xx0319616
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$a Genetic testing in children enrolled in epilepsy surgery program. A real-life study / $c B. Straka, B. Splitkova, M. Vlckova, P. Tesner, H. Rezacova, L. Krskova, M. Koblizek, M. Kyncl, A. Maulisova, K. Bukacova, A. Uhrova-Meszarosova, A. Musilova, M. Kudr, M. Ebel, A. Belohlavkova, A. Jahodova, P. Liby, M. Tichy, P. Jezdik, J. Zamecnik, E. Aronica, P. Krsek
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$a OBJECTIVE: Although genetic causes of drug-resistant focal epilepsy and selected focal malformations of cortical development (MCD) have been described, a limited number of studies comprehensively analysed genetic diagnoses in patients undergoing pre-surgical evaluation, their outcomes and the effect of genetic diagnosis on surgical strategy. METHODS: We analysed a prospective cohort of children enrolled in epilepsy surgery program over January 2018-July 2022. The majority of patients underwent germline and/or somatic genetic testing. We searched for predictors of surgical outcome and positive result of germline genetic testing. RESULTS: Ninety-five patients were enrolled in epilepsy surgery program and 64 underwent resective epilepsy surgery. We ascertained germline genetic diagnosis in 13/74 patients having underwent germline gene testing (pathogenic or likely pathogenic variants in CHRNA4, NPRL3, DEPDC5, FGF12, GRIA2, SZT2, STXBP1) and identified three copy number variants. Thirty-five patients underwent somatic gene testing; we detected 10 pathogenic or likely pathogenic variants in genes SLC35A2, PTEN, MTOR, DEPDC5, NPRL3. Germline genetic diagnosis was significantly associated with the diagnosis of focal epilepsy with unknown seizure onset. SIGNIFICANCE: Germline and somatic gene testing can ascertain a definite genetic diagnosis in a significant subgroup of patients in epilepsy surgery programs. Diagnosis of focal genetic epilepsy may tip the scales against the decision to proceed with invasive EEG study or surgical resection; however, selected patients with genetic focal epilepsies associated with MCD may benefit from resective epilepsy surgery and therefore, a genetic diagnosis does not disqualify patients from presurgical evaluation and epilepsy surgery.
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$a Splitkova, Barbora $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: barbora.splitkova@fnmotol.cz
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$a Vlckova, Marketa $u Department of Biology and Medical Genetics, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: marketa.vlckova@fnmotol.cz
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$a Tesner, Pavel $u Department of Biology and Medical Genetics, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: pavel.tesner@fnmotol.cz
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$a Rezacova, Hana $u Department of Biology and Medical Genetics, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: hana.rezacova@fnmotol.cz
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$a Krskova, Lenka $u Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: lenka.krskova@fnmotol.cz
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$a Koblizek, Miroslav $u Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: miroslav.koblizek@fnmotol.cz
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$a Kyncl, Martin $u Department of Radiology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: martin.kyncl@fnmotol.cz
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$a Maulisova, Alice $u Department of Clinical Psychology, Motol University Hospital, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: alice.maulisova@fnmotol.cz
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$a Bukacova, Katerina $u Department of Clinical Psychology, Motol University Hospital, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: katerina.bukacova@fnmotol.cz
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$a Uhrova-Meszarosova, Anna $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: Anna.Meszarosova@seznam.cz
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$a Musilova, Alena $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: alena.musilova@lfmotol.cuni.cz
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$a Kudr, Martin $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: martin.kudr@fnmotol.cz
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$a Ebel, Matyas $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: matyas.ebel@fnmotol.cz
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$a Belohlavkova, Anezka $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: anezka.belohlavkova@fnmotol.cz
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$a Jahodova, Alena $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: alena.jahodova@fnmotol.cz
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$a Liby, Petr $u Department of Neurosurgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: petr.liby@fnmotol.cz
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$a Tichy, Michal $u Department of Neurosurgery, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: michal.tichy@fnmotol.cz
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$a Jezdik, Petr $u Faculty of Electrical Engineering, Department of Circuit Theory, Czech Technical University in Prague, Technicka 2, Praha 6, 166 27, Czech Republic. Electronic address: jezdip1@fel.cvut.cz
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$a Zamecnik, Josef $u Department of Pathology and Molecular Medicine, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: josef.zamecnik@fnmotol.cz
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$a Aronica, Eleonora $u Amsterdam UMC Location University of Amsterdam, Department of Neuropathology, Amsterdam Neuroscience, the Netherlands; Stichting Epilepsie Instellingen Nederland (SEIN), Heemstede, the Netherlands. Electronic address: e.aronica@amsterdamumc.nl
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$a Krsek, Pavel $u Department of Paediatric Neurology, Motol Epilepsy Center, 2nd Faculty of Medicine, Charles University and Motol University Hospital, Full Member of the ERN EpiCARE, V Uvalu 84, 15006, Prague, Czech Republic. Electronic address: pavel.krsek@post.cz
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