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Genes in infantile epileptic encephalopathies.


Depienne C1,2,3, Gourfinkel-An I2,3,4,5, Baulac S2,3, LeGuern E1,2,3.


Jasper's Basic Mechanisms of the Epilepsies [Internet]. 4th edition. Bethesda (MD): National Center for Biotechnology Information (US); 2012.

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Unité Fonctionnelle de Neurogénétique Moléculaire et cellulaire, Département de Génétique et Cytogénétique, Centre de Génétique Moléculaire et chromosomique, AP-HP, GH Pitié-Salpêtrière, Paris, France
INSERM U 975, Paris, France
Université Pierre et Marie Curie, Centre de Recherche de l’institut du cerveau et de la moelle épinière, UMR_S975 Paris, France
Pôle d’Epileptologie, AP-HP, Groupe Hospitalier Pitié-Salpêtrière, Paris, France
Centre de référence épilepsies rares, Paris, France


Infantile epileptic encephalopathies, such as Dravet syndrome, Ohtahara syndrome, West syndrome, Lennox-Gastaut syndrome, myoclonic-astatic epilepsy, and Landau-Kleffner syndrome, are devastating epilepsies. Cases are often sporadic or patients have only a limited family history of epilepsy. Although a complex inheritance has long been suspected in epilepsy, recent data indicate that many sporadic rare epileptic disorders, such as Dravet syndrome, CDKL5/STK9 Rett-like epileptic encephalopathy, ARX-related epilepsies, SRPX2-related rolandic epilepsy associated with oral and speech dyspraxia and mental retardation, and STXBP1-related West/Ohtahara syndromes, are due to a mutation in a unique gene. Dravet syndrome, for example, is mainly due to de novo mutations in SCN1A, the gene encoding the voltage-gated neuronal sodium channel alpha 1 subunit, which explains why most patients are isolated cases. All types of mutations are observed: missense mutations, premature termination codon and intragenic rearrangements. This large mutation spectrum contrasts with that of generalized epilepsy with febrile seizures plus (GEFS+), an autosomal dominant condition also characterized by febrile and afebrile seizures but with a usually benign outcome, in which only missense mutations are found. Recently, mutations in PCDH19, encoding protocadherin 19 on chromosome X, were identified in females with an EFMR or Dravet-like phenotype. Heterozygous females are affected while hemizygous males are spared, this unusual inheritance probably being due to a mechanism called cellular interference. The genetic data accumulated for Dravet syndrome and other related disorders have to be kept in mind when studying epileptic encephalopathies.

Copyright © 2012, Michael A Rogawski, Antonio V Delgado-Escueta, Jeffrey L Noebels, Massimo Avoli and Richard W Olsen.

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