Vol. 29/2020 Issue 59
okładka czasopisma Child Neurology
powiększenie okładki
Journal Info

CHILD NEUROLOGY

Journal of the Polish Society of Child Neurologists

PL ISSN 1230-3690
e-ISSN 2451-1897
DOI 10.20966
Semiannual


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Spektrum zespołów padaczkowych i padaczek uogólnionych z drgawkami gorączkowymi plus (GEFS+) zależnych od mutacji w genie SCN1A


SCN1A – related spectrum of generalized epilepsy syndromes and epilepsy with febrile seizures plus




1Klinika Neurologii Dzieci i Młodzieży,
2Zakład Genetyki Medycznej Instytut Matki i Dziecka w Warszawie

Neurol Dziec 2009; 18, 36: 41-46
Full text PDF Spektrum zespołów padaczkowych i padaczek uogólnionych z drgawkami
gorączkowymi plus (GEFS+



STRESZCZENIE
Mutacje w genie kodującym podjednostkę alfa1 kanału sodowego (SCN1A) powiązane są z różnymi typami padaczek. Dotychczas zostało zidentyfikowanych ponad 500 nowych mutacji. Kliniczne spektrum zaburzeń zależnych od mutacji w genie SCN1A obejmuje względnie łagodne padaczki uogólnione z drgawkami gorączkowymi plus do ciężkich zespołów padaczkowych, takich jak ciężka miokloniczna padaczka niemowląt i lekooporna padaczka dziecięca z napadami toniczno-klonicznymi. Mutacja w SCN1A została znaleziona także u pojedynczych chorych z innymi zespołami padaczkowymi (np. zespół Westa, zespół Lennoxa-Gastaut, zapalenie mózgu Rasmussena, zespół Panayiotopolousa) oraz w rzadkich przypadkach rodzinnej migreny połowiczoporaźnej i rodzinnego autyzmu. Identyfikacja defektu molekularnego, zwłaszcza w przypadku lekoopornych padaczek, umożliwia potwierdzenie rozpoznania na gruncie klinicznym, ustalenie rokowania, uniknięcie prowadzenia niepotrzebnej diagnostyki oraz wybór odpowiedniego leczenia.

Słowa kluczowe: padaczka, drgawki gorączkowe, SCN1A, GEFS+, ciężka miokloniczna padaczka niemowląt, kanałopatie


ABSTRACT
Mutations in the gene coding for the α1 subunit of the neuronal sodium channel (SCN1A) have been associated with various types of epilepsy. So far more than 500 new mutations have been identified. Clinical spectrum of SCN1A mutations ranges from quite benign generalized epilepsy with febrile seizures plus (GEFS+) to severe epilepsy syndromes such as severe myoclonic epilepsy of infancy and intractable childhood epilepsy with generalized tonic-clonic seizures. SCN1A mutations have been also found in single patients with other epilepsy syndromes (e.g West syndrome, Lennox-Gastaut syndrome, Rasmussen encephalitis and Panayiotopoulos syndrome) and in rare cases of Familial Hemiplegic Migraine and Familial Autism as well. Identification of the molecular defect, especially in the case of refractory epilepsies, confirms clinical diagnosis, provides information on prognosis and allows to avoid unnecessary investigations and to select appropriate management.

Key words: epilepsy, febrile seizures, SCN1A, GEFS+, Severe myoclonic epilepsy in infancy, channalopathy


PIŚMIENNICTWO
[1] 
Graves T.D., Hanna M.G.: Channeling into epilepsies. Epilepsy Currents 2008;8(2):37-38
[2] 
Engel J Jr: ILAE Commission Report. A Proposed Diagnostic Scheme for People with Epileptic Seizures and with Epilepsy: Report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42(6):796-80
[3] 
OMIM (TM Online Mendelian Inheritance in Man). McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University (Baltimore, MD) and National Center for Biotechnology Information, National Library of Medicine (Bethesda, MD). www.ncbi.nlm.nih.gov/omim/ (05.2009)
[4] 
Scheffer I.E., Berkovic S.F.: Generalized epilepsy with febrile seizures plus. A genetic disorder with heterogeneous clinical phenotypes. Brain 1997;120 3:479-90.
[5] 
Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis. International League Against Epilepsy. Epilepsia 1993;34:592-596
[6] 
Singh R., Scheffer I.E., Crossland K. et al.: Generalized epilepsy with febrile seizures plus: a common childhood-onset genetic epilepsy syndrome. Ann Neurol 1999;45:75-81.
[7] 
Wallace R.H., Wang D.W., Singh R. et al.: Febrile seizures and generalized epilepsy associated with a mutation in the Na+-channel beta1 subunit gene SCN1B. Nat Genet 1998;19:366-370.
[8] 
Audenaert D., Claes L., Ceulemans B. et al.: A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology 2003;61:854-856.
[9] 
Audenaert D., van Broeckhoven C., de Jonghe P.: Genes and loci involved in febrile seizures and related epilepsy syndromes. Hum Mutat 2006;27(5):391-401.
[10] 
Pineda-Trujillo N., Carrizosa J., Cornejo W.: A novel SCN1A mutation associated with severe GEFS+ in a large South American pedigree. Seizure 2005;14:123-128.
[11] 
Baulac S., Gourfinkel An. I., Couarch P. et al.: A novel locus for generalized epilepsy with febrile seizures plus in French families. Arch Neurol 2008;65:943-951.
[12] 
Escaya A., MacDonald B.T., Meisler M.H. et al.: Mutations of SCN1A, encoding a neuronal sodium channel, in two families with GEFS+2. Nat Genet 2000;24:343-345.
[13] 
Escaya A., Heils A., MacDonald B.T. et al.: A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus-and prevalence of variants in patients with epilepsy. Am J Hum Genet 2001;68:866-873.
[14] 
Yamakawa K.: Na channel gene mutations In epilepsy-The functional consequences. Epilepsy Research 2006;70:S 218-222.
[15] 
Wallace R.H., Scheffer I.E., Barnett S. et al.: Neuronal sodium-channel alpha1-subunit mutations in generalized epilepsy with febrile seizures plus. Am J Hum Genet 2001;68:859-65.
[16] 
Claes L., Del-Favero J., Ceulemans B. et al.: De novo mutations in the sodium-channel gene SCN1A causa severe myoclonic epilepsy of infancy. Am J Hum Genet 2001;68:1327-1332.
[17] 
Miller I.O., de Menez M.A.S.: SCN1A-Related Seizure Disorders. GeneReviews 2007; GeneTests www.genetest.org (GeneTests: Medical Genetics Information Resource. Copyright, University of Washington, Seattle. 1993-2009; 05.2009).
[18] 
Mulley J.C., Scheffer I.E., Petrou S. et al.: SCN1A mutations and epilepsy. Hum Mutat 2005;25:535-542.
[19] 
Berkovic S.F., Harkin L., McMahon J.M. et al.: De-novo mutations of the sodium channel gene SCN1A in alleged vaccine encephalopathy: a retrospective study. Lancet Neurol 2006;5:488-492.
[20] 
Colosimo E., Gambardella A., Mantegazza M. et al.: Electroclinical Features of a family with Simple febr ile seizures and temporal lobe epilepsy associated with SCN1A loss-of-function mutation. Epilepsia 2007;48(9):1691-1696.
[21] 
Grosso S., Orrico A., Galli L. et al.: SCN1A mutation associated with atypical Panayiotopoulos syndrome. Neurology 2007;69:609-611.
[22] 
Ohmori L., Ouchida M., Kobayashi K. et al.: Rasmussen encephalitis associated with SCN1A mutation. Epilepsia 2008;49(3):521-526.
[23] 
Dichgans M., Freilinger T., Eckstein G. et al.: Mutation in the neuronal voltage-gated sodium channel SCN1A In familial hemiplegic migraine. Lancet 2005;366:371-377.
[24] 
Weiss L.A., Escayg A., Kearney J.A. et al.: Sodium channels SCN1A, SCN2A and SCN3A in familial autism. Mol Psychiatry 2003;8:186-194.
[25] 
Dravet C., Bureau M., Oguni H. et al.: Severe myoclonic epilepsy in infancy. [w:] Roger J., Bureau M., Dravet C. et al.:Epileptic Syndromes in Infancy, Childhood and Adolescence, 3 ed. John Libbey, Eastligh 2002;81-103.
[26] 
Nabbout R., Gennaro E., Dalla Bernardina B. et al.: Spectrum of SCN1A mutations in severe myoclonic epilepsy of infancy. Neurology 2003;60:1961-1967.
[27] 
Hattori J., Ouchida M., Ono J., Miyake S. et al.: A screening test for the prediction of Dravet syndrome before one year of age. Epilepsia 2008;49 (4):626-633.
[28] 
Fukuma G., Oguni H., Shirasaka Y. et al.: Mutations of neuronal voltagegated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB). Epilepsia 2004;45:140-148.
[29] 
Fujiwara T.: Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies. Epilepsy Res 2006;1:S223-230.
[30] 
Doose H., Lunau H., Castiglione et al.: Severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 1998;29:229-238.
[31] 
Bonanni P., Malcarne M., Moro F. et al.: Generalized epilepsy with febrile seizures plus (GEFS+): clinical spectrum in seven Italian families unrelated to SCN1A, SCN1B, and GABRG2 gene mutations. Epilepsia 2004;45:149-158.
[32] 
Fujiwara T., Sugawara T., Mazaki-Miyazaki E. et al.: Mutations of sodium channel alpha subunit type 1 (SCN1A) in intractable childhood epilepsies with frequent generalized tonic-clonic seizures. Brain 2003;126:531- 546.
[33] 
Ebach K., Joos H., Doose H. et al.: SCN1A mutation analysis in myoclonic astatic epilepsy and severe idiopathic generalized epilepsy of infancy with generalized tonic-clonic seizures. Neuropediatrics 2005;36:210- 213.
[34] 
Baulac S., Gourfinkel-An I., Picard F. et al.: A second locus for familial generalized epilepsy with febrile seizures plus maps to chromosome 2q21-q33. Am J Hum Genet 1999;65:1078-1085.
[35] 
Elektroniczne bazy danych mutacji genu SCN1A: SCN1AVDB (The Variation Database of SCN1A) www.molgen.ua.ac.be/SCN1AMutations VIB - Department of Molecular Genetics; University of Antwerp (2008) SCN1A infobase http://web.scn1a.info UC Davis Medical Center, Department of Neurology; Lossin C. (2008) A catalog of SCN1A variants. Brain and Development 31;114-130, (05.2009)
[36] 
Mulley J.C., Nelson P., Guerrero S. et al.: A new molecular mechanism for severe myoclonic epilepsy of infancy: exonicdeletions in SCN1A. Neurology 2006;26;67(6):1094-1095.
[37] 
Madia F., Striano P., Gennaro E. et al.: Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy. Neurology 2006;10;67(7):1230-1235.
[38] 
Marini C., Mei D., Temudo T. et al.: Idiopathic epilepsies with seizures precipitated by fever and SCN1A abnormalities. Epilepsia 2007;48(9):1678-1685.
[39] 
Wang J.W., Kurahashi H., Ishii A. et al.: Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy. Epilepsia 2008;49(9):1528-1534.
[40] 
Marini C., Scheffer I., Nabbout R. et al.: SCN1A duplications and deletions detected in Dravet syndrome: Implications for molecular diagnosis. Epilepsia 2009; Epub ahead of print.
[41] 
Rhodes T.H., Vanoye C.G., Ohmori I. et al.: Sodium Channel dysfunction in intractable childhood epilepsy with generalized tonic-clonic seizures. J Physiol 2005;569.2:433-445.
[42] 
Ragsdale D.S.: How do mutant Nav1.1 sodium channel cause epilepsy? Brain Res Rev 2008; doi:10.1016/j.brainresrev.2008.01.003.
[43] 
Gambardella A., Marini C.: Clinical spectrum of SCN1A mutations. Epilepsia 2009;50(S.5): 20-23.
[44] 
Delgado-Escueta A.V., Bourgeois B.F.D.: Debate: Does genetic information in human help us treat patients? Progenetic information in human help us treat patients, con-genetic information does not help at all. Epilepsia 2008;49(S9):13-24.
[45] 
Morimoto M., Mazaki E., Nishimura A. et al.: SCN1A mutation mosaicism in a family with severe myoclonic epilepsy in infancy. Epilepsia 2006;47(10):1732-1736.
[46] 
Gennaro E., Santorelli F.M., Bertini E. et al.: Somatic and germline mosaicisms in severe myoclonic epilepsy of infancy. Biochem Biophys Res Commun 2006;341(2):489-930.
[47] 
Marini C., Mei D., Helen Cross J. et al.: Mosaic SCN1A mutation in familial severe myoclonic epilepsy of infancy. Epilepsia 2006;47(10):1737- 1740.
[48] 
Yu F.H., Mantegazza M., Westenbroek R.E. et al.: Reduced sodium current in GABAergic interneurons in a Mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 2006;9:1142-1149.
[49] 
Chiron C., Marchand M.C., Tran A. et al.: Stiripentol in severe myoclonic epilepsy in infancy: a randomised placebo-controlled syndromededicated trial. STICLO study group. Lancet 2000;356:1638-1642.
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