Genetic Generalized Epilepsies

  • Aglaia VignoliEmail author
  • Maria Paola Canevini


The purpose of this chapter is to delineate the clinical and EEG features of the genetic generalized epilepsies, which are a heterogeneous group of conditions, linked by strict criteria. Both the EEG and seizure characteristics may be helpful in the clinical management of patients and avoid unuseful therapies and diagnostic procedures.


Genetic generalized epilepsies Childhood absence epilepsy Juvenile absence epilepsy Juvenile myoclonic epilepsy Epilepsy with generalized seizures alone Eyelid myoclonia with absences 

Supplementary material

Video 1

In the video, the girl has an initial brief eyelid flickering; she remains completely unresponsive from the beginning to the terminal phase of the discharge (MP4 10078 kb)

Video 2

Video recording of a child with CAE: the ictal discharge is related to a complete loss of awareness and automatisms, which end at the end of the seizure (MP4 9758 kb)

Video 3

JME ictal recording of a 9-year-old boy at morning awakening. Several generalized PSW discharges associated with bilateral jerks are recorded (MP4 6914 kb)


  1. 1.
    Scheffer IE, Berkovic S, Capovilla G, Connolly MB, French J, Guilhoto L, et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):512–21. Scholar
  2. 2.
    Ottman R. Genetic epidemiology of epilepsy. Epidemiol Rev. 1997;19:120–8.CrossRefGoogle Scholar
  3. 3.
    Kobow K, Blümcke I. Epigenetics in epilepsy. Neurosci Lett. 2018;667:40–6. Scholar
  4. 4.
    Scheffer IE, Mefford HC. Epilepsy: beyond the single nucleotide variant in epilepsy genetics. Nat Rev Neurol. 2014;10(9):490–1. Scholar
  5. 5.
    Mullen SA, Berkovic S, ILAE Genetics Commission. Genetic generalized epilepsies. Epilepsia. 2018;59:1148–53. Scholar
  6. 6.
    Nuyts S, D’Souza W, Bowden SC, Vogrin SJ. Structural brain abnormalities in genetic generalized epilepsies: a systematic review and meta-analysis. Epilepsia. 2017;58(12):2025–37. Scholar
  7. 7.
    Gloor P. Generalized cortico-reticular epilepsies. Some considerations on the pathophysiology of generalized bilaterally synchronous spike and wave discharge. Epilepsia. 1968;9(3):249–63.CrossRefGoogle Scholar
  8. 8.
    Polack PO, Mahon S, Chavez M, Charpier S. Inactivation of the somatosensory cortex prevents paroxysmal oscillations in cortical and related thalamic neurons in a genetic model of absence epilepsy. Cereb Cortex. 2009;19(9):2078–91. Scholar
  9. 9.
    Meeren H, van Luijtelaar G, Lopes da Silva F, Coenen A. Evolving concepts on the pathophysiology of absence seizures: the cortical focus theory. Arch Neurol. 2005;62(3):371–6.CrossRefGoogle Scholar
  10. 10.
    Wolf P, Beniczky S. Understanding ictogenesis in generalized epilepsies. Expert Rev Neurother. 2014;14(7):787–98. Scholar
  11. 11.
    Norden AD, Blumenfeld H. The role of subcortical structures in human epilepsy. Epilepsy Behav. 2002;3(3):219–31.CrossRefGoogle Scholar
  12. 12.
    Luo C, Li Q, Xia Y, Lei X, Xue K, Yao Z, et al. Resting state basal ganglia network in idiopathic generalized epilepsy. Hum Brain Mapp. 2012;33(6):1279–94. Scholar
  13. 13.
    Roger J, Bureau M, Ferrer-Vidal LO, Daurella LO, Saltarelli A, Genton P. Clinical and electroencephalographic characteristics of idiopathic generalized epilepsies. In: Malafosse A, Genton P, Hirsch E, et al., editors. Idiopathic generalized epilepsies: clinical, experimental and genetic aspects. London: John Libbey; 1994.Google Scholar
  14. 14.
    Kasteleijn-Nolst Trenite DGA, Hirsch E, Takahashi T. Photosensitivity, visual induced seizures and epileptic syndromes. In: Roger J, Bureau M, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 2002.Google Scholar
  15. 15.
    Koutroumanidis M, Arzimanoglou A, Caraballo R, Goyal S, Kaminska A, Laoprasert P, et al. The role of EEG in the diagnosis and classification of the epilepsy syndromes: a tool for clinical practice by the ILAE Neurophysiology Task Force (Part 1). Epileptic Disord. 2017;19(3):233–98. Scholar
  16. 16.
    Loiseau P. Absence epilepsy. In: Roger J, Dravet C, Bureau M, Dreifuss FE, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 1992.Google Scholar
  17. 17.
    Penry JK, Porter RJ, Dreifuss RE. Simultaneous recording of absence seizures with video tape and electroencephalography. A study of 374 seizures in 48 patients. Brain. 1975;98(3):427–40.CrossRefGoogle Scholar
  18. 18.
    Trinka E, Baumgartner S, Unterberger I, Unterrainer J, Luef G, Haberlandt E, Bauer G. Long-term prognosis for childhood and juvenile absence epilepsy. J Neurol. 2004;251(10):1235–41.CrossRefGoogle Scholar
  19. 19.
    Grosso S, Galimberti D, Vezzosi P, Farnetani M, Di Bartolo RM, Bazzotti S, et al. Childhood absence epilepsy: evolution and prognostic factors. Epilepsia. 2005;46(11):1796–801.CrossRefGoogle Scholar
  20. 20.
    Callenbach PM, Bouma PA, Geerts AT, Arts WF, Stroink H, Peeters EA, et al. Long-term outcome of childhood absence epilepsy: Dutch Study of Epilepsy in Childhood. Epilepsy Res. 2009;83(2–3):249–56. Scholar
  21. 21.
    Cobb W. EEG interpretation in clinical medicine. Part B. In: Remond A, editor. Handbook of electroencephalography and clinical neurophysiology. Amsterdam: Elsevier; 1976.Google Scholar
  22. 22.
    Loiseau P, Duche B. Childhood absence epilepsy. In: Duncan JS, Panayiotopoulos CP, editors. Typical absences and related epileptic syndromes. Edinburgh: Churchill Livingstone; 1995.Google Scholar
  23. 23.
    Dalla Bernardina B, Sgrò V, Fejerman N. Epilepsy with centro-temporal spikes and related syndromes in:. “Epileptic syndromes in infancy, childhood and adolescence”, Roger J, Bureau M, Dravet CH, Genton P, Tassinari CA, Wolf P (John Libbey, London, 2002.Google Scholar
  24. 24.
    Hirsch E, Blanc-Platier A, Marescaux C. What are the relevant criteria for a better classification of epileptic syndromes with typical absences? In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies: clinical experimental and genetic aspects. London: John Libbey; 1994.Google Scholar
  25. 25.
    Panayiotopoulos CP. Absence epilepsies. In: Engel J, Pedley TA, editors. Epilepsy. A comprehensive textbook. Philadelphia: Lippincott-Raven; 1997.Google Scholar
  26. 26.
    Gelisse P, Wolf P, Inoue Y. Juvenile absence epilepsy. In: Bureau M, Genton P, Dravet C, Delgado-Escueta A, Tassinari CA, Thomas P, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. 5th ed. London: John Libbey Eurotext; 2012.Google Scholar
  27. 27.
    Marini C, Scheffer IE, Crossland KM, Grinton BE, Phillips FL, McMahon JM, et al. Genetic architecture of idiopathic generalized epilepsy: clinical genetic analysis of 55 multiplex families. Epilepsia. 2004;45(5):467–78.CrossRefGoogle Scholar
  28. 28.
    Wolf P, Inoue Y. Therapeutic response of absence seizures in patients of an epilepsy clinic for adolescents and adults. J Neurol. 1984;231:225–9.CrossRefGoogle Scholar
  29. 29.
    Wolf P, Inoue Y. Juvenile absence epilepsy. In: Roger J, Bureau M, Dravet CH, et al., editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 2002.Google Scholar
  30. 30.
    Panayiotoupolos CP, Obeid T, Waheed G. Differentiation of typical absence seizures in epileptic syndromes. Brain. 1989;112:1039–56.CrossRefGoogle Scholar
  31. 31.
    Sgrò V, Canevini MP, Lastrico A, Guidolin L, Vignoli A, Saltarelli A, et al. Assenze tipiche: analisi elettroclinica di 37 pazienti con epilessia-assenza dell’infanzia o dell’adolescenza. Aggiornamenti in Epilettologia. Boll Lega It Epil. 1995;91/92:97–9.Google Scholar
  32. 32.
    Thomas P, Valton L, Genton P. Absence and myoclonic status epilepticus precipitated by antiepileptic drugs in idiopathic generalized epilepsy. Brain. 2006;129(Pt 5):1281–92.CrossRefGoogle Scholar
  33. 33.
    Janz D, Christian W. Impulsiv petit mal. Dtsch Z Nervenheilk. 1957;176:346–86.CrossRefGoogle Scholar
  34. 34.
    Yacubian EM. Juvenile myoclonic epilepsy: challenges on its 60th anniversary. Seizure. 2017;44:48–52. Scholar
  35. 35.
    Delgado-Escueta AV, Koeleman BP, Bailey JN, Medina MT, Durón RM. The quest for juvenile myoclonic epilepsy genes. Epilepsy Behav. 2013;28(Suppl 1):S52–7. ReviewCrossRefPubMedGoogle Scholar
  36. 36.
    Thomas P, Genton P, Gelisse P, Medina M, Serafini A. Juvenile myoclonic epilepsy. In: Bureau M, Genton P, Dravet C, Delgado-Escueta A, Tassinari CA, Thomas P, Wolf P, editors. Epileptic syndromes in infancy, childhood and adolescence. London: John Libbey; 2012.Google Scholar
  37. 37.
    Janz D, Cristian W. Impulsive Petit Mal (traduction anglaise par P Genton). In: Malafosse A, Genton P, Hirsch E, Marescaux C, Broglin D, Bernasconi R, editors. Idiopathic generalized epilepsies: clinical, experimental and genetic aspects. London: John Libbey; 1994.Google Scholar
  38. 38.
    Canevini MP, Mai R, Di Marco C, Bertin C, Minotti L, Pontrelli V, et al. Juvenile myoclonic epilepsy of Janz: clinical observations in 60 patients. Seizure. 1992;1(4):291–8.CrossRefGoogle Scholar
  39. 39.
    Striano S, Capovilla G, Sofia V, Romeo A, Rubboli G, Striano P, et al. Eyelid myoclonia with absences (Jeavons syndrome): a well-defined idiopathic generalized epilepsy syndrome or a spectrum of photosensitive conditions? Epilepsia. 2009;50(Suppl 5):15–9. Scholar
  40. 40.
    Kasteleijn-Nolst Trenité DG, Schmitz B, Janz D, Delgado-Escueta AV, Thomas P, Hirsch E, et al. Consensus on diagnosis and management of JME: from founder’s observations to current trends. Epilepsy Behav. 2013;28(Suppl 1):S87–90. Scholar
  41. 41.
    Inoue Y, Seino M, Kubota H, Yamakaku K, Tanaka M, Yagi K. Epilepsy with praxis-induced seizures. In: Wolf P, editor. Epileptic seizures and syndromes. London: John Libbey; 1994.Google Scholar
  42. 42.
    Vollmar C, O’Muircheartaigh J, Barker GJ, Symms MR, Thompson P, Kumari V, et al. Motor system hyperconnectivity in juvenile myoclonic epilepsy: a cognitive functional magnetic resonance imaging study. Brain. 2011;134.(Pt 6:1710–9. Scholar
  43. 43.
    Park KI, Lee SK, Chu K, Lee JJ, Kim DW, Nam H. The value of video-EEG monitoring to diagnose juvenile myoclonic epilepsy. Seizure. 2009;18(2):94–9. Scholar
  44. 44.
    Canevini MP, Sgrò V, Canger R. Le assenze nell’epilessia mioclonica giovanile. Boll Lega It Epil. 1995;91/92:39–42.Google Scholar
  45. 45.
    Panzica F, Rubboli G, Franceschetti S, Avanzini G, Meletti S, Pozzi A, et al. Cortical myoclonus in Janz syndrome. Clin Neurophysiol. 2001;112(10):1803–9.CrossRefGoogle Scholar
  46. 46.
    Lombroso CT. Consistent EEG focalities detected in subjects with primary generalized epilepsies monitored for two decades. Epilepsia. 1997;38:797–812.CrossRefGoogle Scholar
  47. 47.
    Janz D, Wolf P. Epilepsy with Grand Mal on awakening. In: Engel J, Pedley TA, editors. Epilepsy a comprehensive textbook. Philadelphia: Lippincott-Raven; 1997.Google Scholar
  48. 48.
    Unterberger I, Trinka E, Luef G, Bauer G. Idiopathic generalized epilepsies with pure grand mal: clinical data and genetics. Epilepsy Res. 2001;44(1):19–25.CrossRefGoogle Scholar
  49. 49.
    Camfield P, Camfield C. Idiopathic generalized epilepsy with generalized tonic-clonic seizures (IGE-GTC): a population-based cohort with >20 year follow up for medical and social outcome. Epilepsy Behav. 2010;18(1–2):61–3. Scholar
  50. 50.
    Janz D. Epilepsy with grand mal on awakening and sleep-waking cycle. Clin Neurophysiol. 2000;111(Suppl 2):S103–10.CrossRefGoogle Scholar
  51. 51.
    Berg AT, Berkovic SF, Brodie MJ, Buchhalter J, Cross JH, van Emde Boas W, et al. Revised terminology and concepts for organization of seizures and epilepsies: report of the ILAE commission on classification and terminology, 2005–2009. Epilepsia. 2010;51(4):676–85. Scholar
  52. 52.
    Fisher RS, Cross JH, French JA, Higurashi N, Hirsch E, Jansen FE, et al. Operational classification of seizure types by the International League Against Epilepsy: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017;58(4):522–30. Scholar
  53. 53.
    Sadleir LG, Vears D, Regan B, Redshaw N, Bleasel A, Scheffer IE. Family studies of individuals with eyelid myoclonia with absences. Epilepsia. 2012;53(12):2141–8. Scholar
  54. 54.
    Tenney JR, Glauser TA. The current state of absence epilepsy: can we have your attention? Epilepsy Curr. 2013;13(3):135–40. Scholar
  55. 55.
    Vaudano AE, Ruggieri A, Tondelli M, Avanzini P, Benuzzi F, Gessaroli G, et al. The visual system in eyelid myoclonia with absences. Ann Neurol. 2014;76(3):412–27. Scholar
  56. 56.
    Giannakodimos S, Panayiotopoulos CP. Eyelid myoclonia with absences in adults: a clinical and video-EEG study. Epilepsia. 1996;37:36–44.CrossRefGoogle Scholar
  57. 57.
    Tomson T, Marson A, Boon P, Canevini MP, Covanis A, Gaily E, Kälviäinen R, Trinka E. Valproate in the treatment of epilepsy in girls and women of childbearing potential. Epilepsia. 2015;56(7):1006–19. Scholar
  58. 58.
    Bourgeois BF. Chronic management of seizures in the syndromes of idiopathic generalized epilepsy. Epilepsia. 2003;44(Suppl 2):27–32.CrossRefGoogle Scholar
  59. 59.
    Marinas A, Villanueva V, Giráldez BG, Molins A, Salas-Puig J, Serratosa JM. Efficacy and tolerability of zonisamide in idiopathic generalized epilepsy. Epileptic Disord. 2009;11(1):61–6. Scholar

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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of Health Sciences, Epilepsy Center—Child and Adolescent Neurology and PsychiatryUniversity of MilanMilanItaly

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