Genetic testing before epilepsy surgery – An exploratory survey and case collection from German epilepsy centers

Boßelmann, Christian; Antonio‐Arce, Victoria San; Schulze‐Bonhage, Andreas; Fauser, Susanne; Zacher, Pia; Mayer, Thomas; Aparicio, Javier Romano; Albers, Kristina; Cloppenborg, Thomas; Kunz, Wolfram S.; Surges, Rainer; Syrbe, Steffen; Weber, Yvonne G.; Wolking, Stefan

doi:10.1016/j.seizure.2021.12.004

Cited by 15 publications

(14 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Eine multizentrische retrospektive Fallserie aus deutschen Epilepsiezentren erbrachte gute Ergebnisse in einigen Fällen mit Tuberöser Sklerose (TSC1/2) oder genetischen hypothalamischen Hamartomen (GLI3, PTEN), während Personen mit Kanalopathien bzw. Synaptopathien eher nicht von einem epilepsiechirurgischen Eingriff profitierten [43]. Zu einem ähnlichen Ergebnis kam ein systematisches Review von Stevelink und Kollegen [44].…”

Section: Genetische Diagnostikunclassified

Genetische Diagnostik der Epilepsien: Empfehlung der Kommission Epilepsie und Genetik der Deutschen Gesellschaft für Epileptologie (DGfE)

et al. 2023

Self Cite

View full text Add to dashboard Cite

ZusammenfassungDie genetische Diagnostik bei an Epilepsie erkrankten Personen ist inzwischen weit verbreitet und unstrittig sinnhaft geworden. Die Kenntnis einer genetischen Ätiologie kann die Identifikation der Diagnose, genetische Beratung, Therapie und Prognoseeinschätzung der Grunderkrankung maßgeblich unterstützen. Methoden der Hochdurchsatz-Sequenzierung erlauben inzwischen eine rasche, umfassende und kosteneffektive Diagnostik. Diese aktuellen Empfehlungen der Kommission „Epilepsie und Genetik“ der Deutschen Gesellschaft für Epileptologie (DGfE) bauen auf den Empfehlungen der International League Against Epilepsie (ILAE) Commission on Genetics auf. Wir bieten einen praxisnahen Überblick über die Indikationsstellung, praktische Umsetzung, Befundbewertung, und Möglichkeiten der Präzisionsmedizin.

show abstract

Section: Genetische Diagnostikunclassified

Genetische Diagnostik der Epilepsien: Empfehlung der Kommission Epilepsie und Genetik der Deutschen Gesellschaft für Epileptologie (DGfE)

et al. 2023

Self Cite

View full text Add to dashboard Cite

show abstract

“…On the other hand, in adults with epilepsy without any of the above-mentioned complementary features, the probability of obtaining causal variants is lower, and genetic testing would not be indicated from the start within a diagnostic context. Nonetheless, this setting might change in future, if the knowledge of genetic background is able to provide management-changing information regarding treatment or prognosis in epilepsies with mixed etiologies, such as in pre-surgical scenarios ( 57 ).…”

Section: Adult Patients With Dees: Who To Testmentioning

confidence: 99%

Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies

Beltrán‐Corbellini

Aledo‐Serrano

Møller³

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.

show abstract

“…Such genetic causes or predisposing factors include germline variants and/or somatic variants identified mainly through analysis of blood samples and/or brain tissue, respectively. In a recent study, channelopathies or mTORopathies were reported as factors influencing negatively surgical outcome 4,5 . The authors further highlighted that in one individual with a poor outcome (Engel class IV) who underwent epilepsy surgery, only postoperatively genetic testing revealed a pathogenic variant in the sodium voltage‐gated channel alpha subunit 1 ( SCN1A ), confirming the diagnosis of Dravet syndrome 4 .…”

Section: Introductionmentioning

confidence: 95%

“…In a recent study, channelopathies or mTORopathies were reported as factors influencing negatively surgical outcome. 4,5 The authors further highlighted that in one individual with a poor outcome (Engel class IV) who underwent epilepsy surgery, only postoperatively genetic testing revealed a pathogenic variant in the sodium voltage-gated channel alpha subunit 1 (SCN1A), confirming the diagnosis of Dravet syndrome. 4 Other germline variants in candidate genes revealed in epilepsy surgery patients were the DEP domain containing 5, GATOR1 subcomplex subunit (DEPDC5) associated with familial focal epilepsy with variable foci, collagen type IV alpha 1 chain (COL4A1) associated with focal epilepsy and intracerebral hemorrhage and NPR3 like, GATOR1 complex subunit (NPRL3) associated with autosomal dominant focal epilepsy.…”

Section: Introductionmentioning

confidence: 99%

“…4,5 The authors further highlighted that in one individual with a poor outcome (Engel class IV) who underwent epilepsy surgery, only postoperatively genetic testing revealed a pathogenic variant in the sodium voltage-gated channel alpha subunit 1 (SCN1A), confirming the diagnosis of Dravet syndrome. 4 Other germline variants in candidate genes revealed in epilepsy surgery patients were the DEP domain containing 5, GATOR1 subcomplex subunit (DEPDC5) associated with familial focal epilepsy with variable foci, collagen type IV alpha 1 chain (COL4A1) associated with focal epilepsy and intracerebral hemorrhage and NPR3 like, GATOR1 complex subunit (NPRL3) associated with autosomal dominant focal epilepsy. 6,7 In addition, somatic variants of various genes in brain tissues are being increasingly identified in developmental lesions such as malformations of cortical development (MCD), focal cortical dysplasia (FCD), hemimegalencephaly (HME), and low-grade developmental tumors like gangliogliomas (GG).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

The importance of routine genetic testing in pediatric epilepsy surgery

Becker,

Makridis,

Abad‐Perez

et al. 2024

Epilepsia Open

View full text Add to dashboard Cite

Genetic variants in relevant genes coexisting with MRI lesions in children with drug‐resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. Still, presurgical evaluation does not include genetic diagnostics routinely. Here, we report our presurgical evaluation algorithm that includes routine genetic testing. We analyzed retrospectively the data of 68 children with DRE operated at a mean age of 7.8 years (IQR: 8.1 years) at our center. In 49 children, genetic test results were available. We identified 21 gene variants (ACMG III: n = 7, ACMG IV: n = 2, ACMG V: n = 12) in 19 patients (45.2%) in the genes TSC1, TSC2, MECP2, DEPDC5, HUWE1, GRIN1, ASH1I, TRIO, KIF5C, CDON, ANKD11, TGFBR2, ATN1, COL4A1, JAK2, KCNQ2, ATP1A2, and GLI3 by whole‐exome sequencing as well as deletions and duplications by array CGH in six patients. While the results did not change the surgery indication, they supported counseling with respect to postoperative chance of seizure freedom and weaning of antiseizure medication (ASM). The presence of genetic findings leads to the postoperative retention of at least one ASM. In our cohort, the International League against Epilepsy (ILAE) seizure outcome did not differ between patients with and without abnormal genetic findings. However, in the 7/68 patients with an unsatisfactory ILAE seizure outcome IV or V 12 months postsurgery, 2 had an abnormal or suspicious genetic finding as a putative explanation for persisting seizures postsurgery, and 3 had received palliative surgery including one TSC patient. This study highlights the importance of genetic testing in children with DRE to address putative underlying germline variants as genetic epilepsy causes or predisposing factors that guide patient and/or parent counseling on a case‐by‐case with respect to their individual chance of postoperative seizure freedom and ASM weaning.Plain Language SummaryGenetic variants in children with drug‐resistant epilepsy (DRE) can negatively influence epilepsy surgery outcomes. However, presurgical evaluation does not include genetic diagnostics routinely. This retrospective study analyzed the genetic testing results of the 68 pediatric patients who received epilepsy surgery in our center. We identified 21 gene variants by whole‐exome sequencing as well as deletions and duplications by array CGH in 6 patients. These results highlight the importance of genetic testing in children with DRE to guide patient and/or parent counseling on a case‐by‐case with respect to their individual chance of postoperative seizure freedom and ASM weaning.

show abstract

Genetic testing before epilepsy surgery – An exploratory survey and case collection from German epilepsy centers

Cited by 15 publications

References 31 publications

Genetische Diagnostik der Epilepsien: Empfehlung der Kommission Epilepsie und Genetik der Deutschen Gesellschaft für Epileptologie (DGfE)

Genetische Diagnostik der Epilepsien: Empfehlung der Kommission Epilepsie und Genetik der Deutschen Gesellschaft für Epileptologie (DGfE)

Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies

The importance of routine genetic testing in pediatric epilepsy surgery

Contact Info

Product

Resources

About