Incorporating epilepsy genetics into clinical practice: a 360°evaluation

NPJ Genomic Medicine
Stephanie OatesDeb K Pal

Abstract

We evaluated a new epilepsy genetic diagnostic and counseling service covering a UK population of 3.5 million. We calculated diagnostic yield, estimated clinical impact, and surveyed referring clinicians and families. We costed alternative investigational pathways for neonatal onset epilepsy. Patients with epilepsy of unknown aetiology onset < 2 years; treatment resistant epilepsy; or familial epilepsy were referred for counseling and testing. We developed NGS panels, performing clinical interpretation with a multidisciplinary team. We held an educational workshop for paediatricians and nurses. We sent questionnaires to referring paediatricians and families. We analysed investigation costs for 16 neonatal epilepsy patients. Of 96 patients, a genetic diagnosis was made in 34% of patients with seizure onset < 2 years, and 4% > 2 years, with turnaround time of 21 days. Pathogenic variants were seen in SCN8A, SCN2A, SCN1A, KCNQ2, HNRNPU, GRIN2A, SYNGAP1, STXBP1, STX1B, CDKL5, CHRNA4, PCDH19 and PIGT. Clinician prediction was poor. Clinicians and families rated the service highly. In neonates, the cost of investigations could be reduced from £9362 to £2838 by performing gene panel earlier and the median diagnostic delay of 3.43 year...Continue Reading

References

Jun 9, 2006·Journal of Genetic Counseling·UNKNOWN National Society of Genetic Counselors' Definition Task ForceJanet L Williams
Aug 26, 2006·Epilepsy & Behavior : E&B·Eylert Brodtkorb, Fabienne Picard
Feb 1, 2008·Brain : a Journal of Neurology·Ingrid E SchefferSamuel F Berkovic
Jun 6, 2009·Archives of Gynecology and Obstetrics·Amer RazaKhalid S Khan
Jul 22, 2010·Nature Reviews. Neurology·Deb K PalWendy K Chung
Sep 13, 2011·International Review of Neurobiology·Louise ParkerMark A Tanouye
Jan 26, 2012·Annals of Neurology·Sarah WeckhuysenPeter de Jonghe
May 23, 2012·Epilepsia·Johannes R LemkeSaskia Biskup
Jul 21, 2012·Progress in Neurobiology·Hannah M GraytonDavid A Collier
Nov 21, 2012·Developmental Medicine and Child Neurology·Andreas BrunklausSameer M Zuberi
Aug 13, 2013·Nature Genetics·Johannes R LemkeSarah von Spiczak
Oct 3, 2013·Human Resources for Health·Julia BluestoneJames BonTempo
Dec 10, 2013·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Anne-Lise PoulatDorothée Ville
Apr 1, 2014·Nature Methods·Jana Marie SchwarzDominik Seelow
Apr 16, 2014·Nature Reviews. Neurology·Annapurna PoduriRuth Ottman
May 2, 2014·Human Molecular Genetics·Jacques L MichaudElsa Rossignol
May 14, 2014·JAMA Neurology·Jason WangJason Y Park
May 23, 2014·European Journal of Human Genetics : EJHG·Erika Della MinaOrsetta Zuffardi
Jan 9, 2015·Neurology·Jan LarsenUNKNOWN EuroEPINOMICS RES Consortium CRP
Mar 6, 2015·Genetics in Medicine : Official Journal of the American College of Medical Genetics·Sue RichardsUNKNOWN ACMG Laboratory Quality Assurance Committee
Mar 25, 2015·Seizure : the Journal of the British Epilepsy Association·R SinghK Lascelles
Mar 31, 2015·Epilepsia·Saadet Mercimek-MahmutogluO Carter Snead
Jun 2, 2015·Frontiers in Neurology·Jacy L Wagnon, Miriam H Meisler
Aug 22, 2015·Epilepsia·Kevin E ChapmanGregory L Holmes
Oct 21, 2015·Molecular Genetics and Genomics : MGG·Marzena Gajecka
Nov 14, 2015·Current Genetic Medicine Reports·Dale MuzzeyCaroline Lieber
Jan 15, 2016·Epilepsia·Alessandra TerraccianoNicola Specchio
Apr 1, 2016·Neurology·Michael S HildebrandHeather C Mefford
May 11, 2016·Neurology·Paolo TinuperRuth Ottman
May 24, 2016·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·G AnandS Jayawant
Jun 1, 2016·BioMed Research International·Charuta JoshiColleen A Campbell
Oct 27, 2016·Molecular Syndromology·Rikke S MøllerHans A Dahl
Nov 23, 2016·Epilepsy Research·Kameryn M ButlerAndrew Escayg
Jan 23, 2017·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·C von StülpnagelI Borggraefe
Aug 2, 2017·JAMA Pediatrics·Anne T BergSookyong Koh
Aug 15, 2017·Nature Reviews. Genetics·Karen EilbeckMark Yandell

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Citations

Mar 24, 2020·Brain : a Journal of Neurology·David Lewis-SmithRhys H Thomas
May 20, 2020·Epilepsia·Katrine M JohannesenRikke S Møller
May 14, 2020·Neuromolecular Medicine·Behrouz ShademanAlireza Nourazarian
Jan 3, 2019·Brain : a Journal of Neurology·Rosie K A Bunton-StasyshynMiriam H Meisler
Oct 6, 2020·Frontiers in Pharmacology·Luis Felipe Santos MenezesElisabeth Ferroni Schwartz
Nov 30, 2019·Frontiers in Neuroscience·Ana Fernández-MarmiesseMargarita Martínez-Atienza
Aug 3, 2019·Cold Spring Harbor Molecular Case Studies·Drew M Thodeson, Jason Y Park
Mar 9, 2019·Annals of Clinical and Translational Neurology·Guido RubboliRikke S Møller
Nov 13, 2019·BMJ : British Medical Journal·Maria-Christina PetropoulosDeb K Pal
Oct 21, 2020·Nature Reviews. Neurology·Rima Nabbout, Mathieu Kuchenbuch
Nov 12, 2020·Seminars in Neurology·David M Ritter, Katherine Holland
Dec 2, 2020·International Journal of Molecular Sciences·C Marcelo Aldaz, Tabish Hussain
Dec 29, 2019·European Journal of Paediatric Neurology : EJPN : Official Journal of the European Paediatric Neurology Society·Joseph D Symonds, Amy McTague
Apr 21, 2021·Genome Medicine·Madelyn A GillentineEvan E Eichler
Oct 26, 2021·Human Cell·Jordan H WhitlockBrittany N Lasseigne

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Datasets Mentioned

BETA
KIAA2022

Methods Mentioned

BETA
exome sequencing
PCR
biopsy

Software Mentioned

SIFT
Amplexa
Exome
ESEfinder
Amplexa Genetics
NNSPlice
POLYphen
Splicesite finder
Torrent suite
ClinVar

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