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Precision medicine and Epilepsy Genetics

Precision medicine and Epilepsy Genetics

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Webinars

January 23, 2021
Language
English
Speaker
  • Rikke Steensbjerre Møller
Cost
Free
Series
ICNTN
CPD/CME Credits
VOD
Yes

Precision medicine and Epilepsy Genetics
Rikke Steensbjerre Møller (Danish Epilepsy Centre, Dianalund)

Professor Rikke Steensbjerre Møller’s main research areas of interest are: gene discovery in neurodevelopmental disorders and epilepsy; electro-clinical characterization of genetic epilepsies; functional characterization of genetic variants to understand their pathomechanisms; genotype-phenotype-pharmacoresponse correlation studies; improvement of existing or develop new personalized therapies for genetic epilepsies

About the webinar

Treatment of epilepsy remains largely empirical, and individual prescribing based on the mechanism of action is generally not possible. However, recent findings in genetic epilepsies have elucidated some mechanisms of epileptogenesis, unravelling the role of a number of genes with different functions, such as ion channels, proteins associated to the vesical synaptic cycle or involved in energy metabolism. The advent of Next Generation Sequencing is providing precision genetics enabling precision medicine in approximately one quarter of patients, which is illustrating the enormous utility of genetic testing for therapeutic decision-making.

Although any patient with refractory epilepsy may benefit from genetic screening, such testing will be of most importance in patients with early-onset seizures (less than 3 years of age), a family history of seizures, associated neurological deficit, or intellectual disability. A major goal of the genetic studies is the identification of novel drug targets and tailored therapies based on the cause of disease. The discovery of specific genetic mutations has also helped us to repurpose drugs with specific actions which may have been used in entirely unrelated conditions. The aim of this presentation is to provide an updated overview of the state-of-the art of precision medicine in those genetic epilepsies in which a precision medicine approach has been already implemented, or in which promising data are under evaluation.

Learning objectives

  • To gain awareness and understanding of genetic causes of epilepsy.
  • To be able to decide which test should be performed in which syndrome
  • To consider precision medicine implications of genetic test results.

References

Baldassari S, Ribierre T, Marsan E, Adle-Biassette H, Ferrand-Sorbets S, Bulteau C | display-authors=etal (2019) Dissecting the genetic basis of focal cortical dysplasia: a large cohort study. Acta Neuropathol 138 (6):885-900. DOI: 10.1007/s00401-019-02061-5 PMID: 31444548.

Berecki G, Bryson A, Terhag J, Maljevic S, Gazina EV, Hill SL | display-authors=etal (2019) SCN1A gain of function in early infantile encephalopathy. Ann Neurol 85 (4):514-525. DOI: 10.1002/ana.25438 PMID: 30779207.

Borlot F, de Almeida BI, Combe SL, Andrade DM, Filloux FM, Myers KA (2019) Clinical utility of multigene panel testing in adults with epilepsy and intellectual disability. Epilepsia 60 (8):1661-1669. DOI: 10.1111/epi.16273 PMID: 31273778.

Brunklaus A, Du J, Steckler F, Ghanty II, Johannesen KM, Fenger CD | display-authors=etal (2020) Biological concepts in human sodium channel epilepsies and their relevance in clinical practice. Epilepsia 61 (3):387-399. DOI: 10.1111/epi.16438 PMID: 32090326.

de Lange IM, Gunning B, Sonsma ACM, van Gemert L, van Kempen M, Verbeek NE | display-authors=etal (2018) Influence of contraindicated medication use on cognitive outcome in Dravet syndrome and age at first afebrile seizure as a clinical predictor in SCN1A-related seizure phenotypes. Epilepsia 59 (6):1154-1165. DOI: 10.1111/epi.14191 PMID: 29750338.

Dilena R, Striano P, Gennaro E, Bassi L, Olivotto S, Tadini L | display-authors=etal (2017) Efficacy of sodium channel blockers in SCN2A early infantile epileptic encephalopathy. Brain Dev 39 (4):345-348. DOI: 10.1016/j.braindev.2016.10.015 PMID: 27876397.

Fitzgerald MP, Fiannacca M, Smith DM, Gertler TS, Gunning B, Syrbe S | display-authors=etal (2019) Treatment Responsiveness in KCNT1-Related Epilepsy. Neurotherapeutics 16 (3):848-857. DOI: 10.1007/s13311-019-00739-y PMID: 31054119.

Gardella E, Møller RS (2019) Phenotypic and genetic spectrum of SCN8A-related disorders, treatment options, and outcomes. Epilepsia 60 Suppl 3 ():S77-S85. DOI: 10.1111/epi.16319 PMID: 31904124.

Gardella E, Marini C, Trivisano M, Fitzgerald MP, Alber M, Howell KB | display-authors=etal (2018) The phenotype of SCN8A developmental and epileptic encephalopathy. Neurology 91 (12):e1112-e1124. DOI: 10.1212/WNL.0000000000006199 PMID: 30171078.

Han Z, Chen C, Christiansen A, Ji S, Lin Q, Anumonwo C | display-authors=etal (2020) Antisense oligonucleotides increase Scn1a expression and reduce seizures and SUDEP incidence in a mouse model of Dravet syndrome. Sci Transl Med 12 (558):. DOI: 10.1126/scitranslmed.aaz6100 PMID: 32848094.

Johannesen KM, Nikanorova N, Marjanovic D, Pavbro A, Larsen LHG, Rubboli G | display-authors=etal (2020) Utility of genetic testing for therapeutic decision-making in adults with epilepsy. Epilepsia 61 (6):1234-1239. DOI: 10.1111/epi.16533 PMID: 32427350.

Lenk GM, Jafar-Nejad P, Hill SF, Huffman LD, Smolen CE, Wagnon JL | display-authors=etal (2020) Scn8a Antisense Oligonucleotide Is Protective in Mouse Models of SCN8A Encephalopathy and Dravet Syndrome. Ann Neurol 87 (3):339-346. DOI: 10.1002/ana.25676 PMID: 31943325.

Lewis-Smith D, Ellis CA, Helbig I, Thomas RH (2020) Early-onset genetic epilepsies reaching adult clinics.Brain 143 (3):e19. DOI: 10.1093/brain/awaa029 PMID: 32203577.

Masnada S, Hedrich UBS, Gardella E, Schubert J, Kaiwar C, Klee EW | display-authors=etal (2017) Clinical spectrum and genotype-phenotype associations of KCNA2-related encephalopathies. Brain 140 (9):2337-2354. DOI: 10.1093/brain/awx184 PMID: 29050392.

Møller RS, Weckhuysen S, Chipaux M, Marsan E, Taly V, Bebin EM | display-authors=etal (2016) Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy. Neurol Genet 2 (6):e118. DOI: 10.1212/NXG.0000000000000118 PMID: 27830187.

Napier KR, Tones M, Simons C, Heussler H, Hunter AA, Cross M | display-authors=etal (2017) A web-based, patient driven registry for Angelman syndrome: the global Angelman syndrome registry. Orphanet J Rare Dis 12 (1):134. DOI: 10.1186/s13023-017-0686-1 PMID: 28764722.

Oyrer J, Maljevic S, Scheffer IE, Berkovic SF, Petrou S, Reid CA (2018) Ion Channels in Genetic Epilepsy: From Genes and Mechanisms to Disease-Targeted Therapies. Pharmacol Rev 70 (1):142-173. DOI: 10.1124/pr.117.014456 PMID: 29263209.

Sanders SJ, Campbell AJ, Cottrell JR, Moller RS, Wagner FF, Auldridge AL | display-authors=etal (2018) Progress in Understanding and Treating SCN2A-Mediated Disorders. Trends Neurosci 41 (7):442-456. DOI: 10.1016/j.tins.2018.03.011 PMID: 29691040.

Symonds JD, Zuberi SM, Stewart K, McLellan A, O'Regan M, MacLeod S | display-authors=etal (2019) Incidence and phenotypes of childhood-onset genetic epilepsies: a prospective population-based national cohort. Brain 142 (8):2303-2318. DOI: 10.1093/brain/awz195 PMID: 31302675.

Syrbe S, Hedrich UBS, Riesch E, Djémié T, Müller S, Møller RS | display-authors=etal (2015) De novo loss- or gain-of-function mutations in KCNA2 cause epileptic encephalopathy. Nat Genet 47 (4):393-399. DOI: 10.1038/ng.3239 PMID: 25751627.

Wirrell EC, Nabbout R (2019) Recent Advances in the Drug Treatment of Dravet Syndrome. CNS Drugs 33 (9):867-881. DOI: 10.1007/s40263-019-00666-8 PMID: 31549357.

Wolff M, Johannesen KM, Hedrich UBS, Masnada S, Rubboli G, Gardella E | display-authors=etal (2017) Genetic and phenotypic heterogeneity suggest therapeutic implications in SCN2A-related disorders. Brain 140 (5):1316-1336. DOI: 10.1093/brain/awx054 PMID: 28379373.

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