Genetische Aspekte bei idiopathischen fokalen Epilepsien

Leitthema
First Online:
Received:
Accepted:

Zusammenfassung

Die genetisch bedingten Formen der idiopathischen fokalen Epilepsien haben aufgrund ihrer Häufigkeit wie der Rolando- und anderen benignen Partialepilepsien einen großen klinischen Stellenwert. Zudem wurden hier die ersten ursächlichen Mutationen in Ionenkanalgenen gefunden, wie z. B. im nikotinischen Acetycholinrezeptor bei der autosomal-dominanten nächtlichen Frontallappenepilepsie oder in spannungsabhängigen Kaliumkanälen bei den benignen Neugeborenenanfällen. Die Genetik hat nicht nur in der Aufklärung der pathophysiologischen Vorgänge der Epilepsien ihren Stellenwert. Sie unterstützt auch die genetische Beratung und kann vereinzelt therapeutische Entscheidungen beeinflussen.

Schlüsselwörter

Ionenkanäle Neurone Mutationen Anfälle Epilepsie 

Genetic aspects of idiopathic focal epilepsies

Abstract

Among idiopathic epilepsies, partial forms with a genetic background are of great clinical importance due to their high incidence, for example for Rolandic epilepsy and other benign partial epilepsy syndromes. In addition, the first disease-causing ion channel mutations have been identified, e.g., mutation of the nicotinic acetylcholine receptor in the case of autosomal dominant nocturnal frontal lobe epilepsy or mutation of two potassium channel subunits in benign neonatal seizures. Genetic analyses of patients with epilepsy contribute not only to a better understanding of the pathophysiology but also help genetic counseling and may also influence therapeutic decisions in selected rare cases.

Keywords

Ion channels Neurons Mutation Seizures Epilepsy 
This is a preview of subscription content, log in to check access.

Notes

Interessenkonflikt

Der korrespondierende Autor gibt an, dass kein Interessenkonflikt besteht.

Literatur

  1. 1.
    Hauser WA, Annegers JF, Rocca WA (1996) Descriptive epidemiology of epilepsy: contributions of population-based studies from Rochester, Minnesota. Mayo Clin Proc 71:576–586PubMedCrossRefGoogle Scholar
  2. 2.
    Freitag CM, May TW, Pfäfflin M (2001) Incidence of epilepsies and epileptic syndromes in children and adolescents: a population-based prospective study in Germany. Epilepsia 42:979–985PubMedCrossRefGoogle Scholar
  3. 3.
    Neubauer BA, Waldegger S, Heinzinger J et al (2008) KCNQ2 and KCNQ3 mutations contribute to different idiopathic epilepsy syndromes. Neurology 71:177–183PubMedCrossRefGoogle Scholar
  4. 4.
    Plouin P (1994) Benign idiopathic neonatal convulsions (familial and non-familial): open questions about these syndromes. In: Wolf P (Hrsg) Epileptic seizures and syndromes. Libbey, London, S 193–201Google Scholar
  5. 5.
    Steinlein OK, Conrad C, Weidner B (2007). Benign familial neonatal convulsions: always benign? Epilepsy Res 73:245–249PubMedCrossRefGoogle Scholar
  6. 6.
    Maljevic S, Wuttke TV, Lerche H (2008) Nervous system KV7 disorders: breakdown of a subthreshold brake. J Physiol 586:1791–1780PubMedCrossRefGoogle Scholar
  7. 7.
    Wuttke TV, Jurkat-Rott K, Paulus W (2007) Peripheral nerve hyperexcitability due to dominant-negative KCNQ2 mutations. Neurology 69:2045–2053PubMedCrossRefGoogle Scholar
  8. 8.
    Hunter J, Maljevic S, Shankar A et al (2006) Subthreshold changes of voltage-dependent activation of the K(V)7.2 channel in neonatal epilepsy. Neurobiol Dis 24:194–201PubMedCrossRefGoogle Scholar
  9. 9.
    Wuttke TV, Seebohm G, Bail S et al (2005) The new anticonvulsant retigabine favors voltage-dependent opening of the Kv7.2 (KCNQ2) channel by binding to its activation gate. Mol Pharmacol 67:1009–1017PubMedCrossRefGoogle Scholar
  10. 10.
    Schenzer A, Friedrich T, Pusch M et al (2005) Molecular determinants of KCNQ (Kv7) K+ channel sensitivity to the anticonvulsant retigabine. J Neurosci 25:5051PubMedCrossRefGoogle Scholar
  11. 11.
    Vigevano F, Fusco L, Di Capua M et al (1992) Benign infantile familial convulsions. Eur J Pediatr 151:608–612PubMedCrossRefGoogle Scholar
  12. 12.
    Guipponi M, Rivier F, Vigevano F et al (1997) Linkage mapping of benign familial infantile convulsions (BFIC) to chromosome 19q. Hum Mol Genet 6:473–477PubMedCrossRefGoogle Scholar
  13. 13.
    Szepetowski P, Rochette J, Berquin P et al (1997) Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16. Am J Hum Genet 61:889–898PubMedCrossRefGoogle Scholar
  14. 14.
    Weber YG, Berger A, Bebek N et al (2004) Benign familial infantile convulsions: linkage to chromosome 16p12-q12 in 14 families. Epilepsia 45:601–609PubMedCrossRefGoogle Scholar
  15. 15.
    Ishii A, Zhang B, Kaneko S, Hirose S (2010) Positive association between benign familial infantile convulsions and LGI4. Brain Dev 32:538–543PubMedCrossRefGoogle Scholar
  16. 16.
    Rochette J, Roll P, Szepetowski P (2008) Genetics of infantile seizures with paroxysmal dyskinesia: the infantile convulsions and choreoathetosis (ICCA) and ICCA-related syndromes. J Med Genet 45:773–779PubMedCrossRefGoogle Scholar
  17. 17.
    Vanmolkot KR, Kors EE, Hottenga JJ et al (2003) Novel mutations in the Na+, K+-ATPase pump gene ATP1A2 associated with familial hemiplegic migraine and benign familial infantile convulsions. Ann Neurol 54:360–366PubMedCrossRefGoogle Scholar
  18. 18.
    Weber YG, Jacob M, Weber G, Lerche H (2008) A BFIS-like syndrome with late onset and febrile seizures: suggestive linkage to chromosome 16p11.2–16q12.1. Epilepsia 49:1959–1964PubMedCrossRefGoogle Scholar
  19. 19.
    Heron SE, Crossland KM, Andermann E et al (2002) Sodium-channel defects in benign familial neonatal-infantile seizures. Lancet 360:851–852PubMedCrossRefGoogle Scholar
  20. 20.
    Scalmani P, Rusconi R, Armatura E et al (2006) Effects in neocortical neurons of mutations of the Na(v)1.2 Na+ channel causing benign familial neonatal-infantile seizures. J Neurosci 26:10100–10109PubMedCrossRefGoogle Scholar
  21. 21.
    Liao Y, Deprez L, Maljevic S et al (2010) Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain 133(Pt 5):1403–1414. Epub 2010 Apr 5PubMedCrossRefGoogle Scholar
  22. 22.
    Taylor I, Berkovic SF, Kivity S, Scheffer IE (2008) Benign occipital epilepsies of childhood: clinical features and genetics. Brain 131:2287–2294PubMedCrossRefGoogle Scholar
  23. 23.
    Grosso S, Orrico A, Galli L et al (2007) SCN1A mutation associated with atypical Panayiotopoulos syndrome. Neurology 69:609–611PubMedCrossRefGoogle Scholar
  24. 24.
    Livingston JH, Cross JH, Mclellan A et al (2009) A novel inherited mutation in the voltage sensor region of SCN1A is associated with Panayiotopoulos syndrome in siblings and generalized epilepsy with febrile seizures plus. J Child Neurol 24:503–508PubMedCrossRefGoogle Scholar
  25. 25.
    Brodtkorb E, Picard F (2006) Tobacco habits modulate autosomal dominant nocturnal frontal lobe epilepsy. Epilepsy Behav 2006 9:515–520CrossRefGoogle Scholar
  26. 26.
    Steinlein OK, Mulley JC, Propping P et al (1995) A missense mutation in the neuronal nicotinic acetylcholine receptor alpha 4 subunit is associated with autosomal dominant nocturnal frontal lobe epilepsy. Nat Genet 11:201–203PubMedCrossRefGoogle Scholar
  27. 27.
    Steinlein OK (2004) Genetic mechanisms that underlie epilepsy. Nat Rev Neurosci 5:443–448CrossRefGoogle Scholar
  28. 28.
    Chen Y, Wu L, Fang Y et al (2009) A novel mutation of the nicotinic acetylcholine receptor gene CHRNA4 in sporadic nocturnal frontal lobe epilepsy. Epilepsy Res 83:152–156PubMedCrossRefGoogle Scholar
  29. 29.
    Díaz-Otero F, Quesada M, Morales_Corraliza J et al (2008) Autosomal dominant nocturnal frontal lobe epilepsy with a mutation in the CHRNB2 gene. Epilepsia 49:516–520PubMedCrossRefGoogle Scholar
  30. 30.
    Aridon P, Marini C, Di Resta C et al (2006) Increased sensitivity of the neuronal nicotinic receptor alpha 2 subunit causes familial epilepsy with nocturnal wandering and ictal fear. Am J Hum Genet 79:342–350PubMedCrossRefGoogle Scholar
  31. 31.
    Hoda JC, Wanischeck, Bertrand D, Steinlein OK (2009) Pleiotropic functional effects of the first epilepsy-associated mutation in the human CHRNA2 gene. FEBS Lett 583:1599–1604PubMedCrossRefGoogle Scholar
  32. 32.
    Hogg RC, Raggenbass M, Bertrand D (2003) Nicotinic acetylcholine receptors: from structure to brain function. Rev Physiol Biochem Pharmacol 147:1–46PubMedCrossRefGoogle Scholar
  33. 33.
    Picard F, Bruel D, Servent D et al (2006) Alteration of the in vivo nicotinic receptor density in ADNFLE patients: a PET study. Brain 129:2047–2060PubMedCrossRefGoogle Scholar
  34. 34.
    Zhu G, Okada M, Yoshida S et al (2008) Rats harboring S284L Chrna4 mutation show attenuation of synaptic and extrasynaptic GABAergic transmission and exhibit the nocturnal frontal lobe epilepsy phenotype. J Neurosci 28:12465–12476PubMedCrossRefGoogle Scholar
  35. 35.
    Teper Y, Whyte D, Cahir E et al (2007) Nicotine-induced dystonic arousal complex in a mouse line harboring a human autosomal-dominant nocturnal frontal lobe epilepsy mutation. J Neurosci 27:10128–10142PubMedCrossRefGoogle Scholar
  36. 36.
    Gambardella A, Labate A, Giallonardo A, Aguglia U (2009) Familial mesial temporal lobe epilepsies: clinical and genetic features. Epilepsia 50 (Suppl 5):55–57PubMedCrossRefGoogle Scholar
  37. 37.
    Claes L, Audenaert D, Deprez L et al (2004) Novel locus on chromosome 12q22-q23.3 responsible for familial temporal lobe epilepsy associated with febrile seizures. J Med Genet 41:710–714PubMedCrossRefGoogle Scholar
  38. 38.
    Hedera P, Blair MA, Andermann E et al (2005) Familial mesial temporal lobe epilepsy maps to chromosome 4q (abstract). Epilepsia 46 (Suppl 6):79–80Google Scholar
  39. 39.
    Kobayashi E, Santos NF, Torres FR et al (2003) Magnetic resonance imaging abnormalities in familial temporal lobe epilepsy with auditory auras. Arch Neurol 60:1546–1551PubMedCrossRefGoogle Scholar
  40. 40.
    Ottman R, Rosenberger L, Bagic A et al (2008) Altered language processing in autosomal dominant partial epilepsy with auditory features. Neurology 1:973–1980Google Scholar
  41. 41.
    Di Bonaventura C, Carni M, Diani E et al (2009) Drug resistant ADLTE and recurrent partial status epilepticus with dysphasic features in a family with a novel LGI1mutation: electroclinical, genetic, and EEG/fMRI findings. Epilepsia 50:2481–2486CrossRefGoogle Scholar
  42. 42.
    Rosanoff MJ, Ottman R (2008) Penetrance of LGI1 mutations in autosomal dominant partial epilepsy with auditory features. Neurology 71:567–571PubMedCrossRefGoogle Scholar
  43. 43.
    Nobile C, Michelucci R, Andreazza S et al (2009) LGI1 mutations in autosomal dominant and sporadic lateral temporal epilepsy. Hum Mutat 30:530–536PubMedCrossRefGoogle Scholar
  44. 44.
    Fukata Y, Adesnik H, Iwanaga T et al (2006) Epilepsy-related ligand/receptor complex LGI1 and ADAM22 regulate synaptic transmission. Science 313:1792–1795PubMedCrossRefGoogle Scholar
  45. 45.
    Schulte U, Thumfart JO, Klöcker N et al (2006) The epilepsy-linked Lgi1 protein assembles into presynaptic Kv1 channels and inhibits inactivation by Kvbeta1. Neuron 49:697–706PubMedCrossRefGoogle Scholar
  46. 46.
    Zhou YD, Lee S, Jin Z (2009) Arrested maturation of excitatory synapses in autosomal dominant lateral temporal lobe epilepsy. Nat Med 15:1208–1214PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2011

Authors and Affiliations

  1. 1.Abteilung Neurologie mit Schwerpunkt EpileptologieHertie Institut für Klinische Hirnforschung,Universitätsklinikum TübingenTübingenDeutschland
  2. 2.Abt. NeuropädiatrieUniversitätsklinikum Gießen und MarburgMarburgDeutschland

Personalised recommendations