title: Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies.
abstract: Severe myoclonic epilepsy in infancy (SMEI) manifests very frequent generalized tonic-clonic seizures (GTC), accompanied by myoclonic seizures, absences and partial seizures [Dravet, C., 1978. Les épilepsie grave de l'enfant. Vie Méd. 8, 543-548; Dravet, C., Roger, J., Bureau, M., Dalla Bernardina, B., 1982. Myoclonic epilepsies in childhood. In: Akimoto, H., Kazamatsuri, H., Seino, M., Ward, A. (Eds.), Advances in Epileptology. Raven Press, New York, pp. 135-140; Dravet, C., Bureau, M., Oguni, H., Fukuyama, Y., Cokar, O., 2002. Severe myoclonic epilepsy of infancy (Dravet syndrome). In: Roger, J., Bureau, M., Dravet, C., Genton, P., Tassinari, C.A., Wolf, P. (Eds.), Epileptic Syndromes in Infancy, Childhood and Adolescence, third ed. John Libbey, London, pp. 81-103]. However, there is a group of severe epilepsy that has many characteristics common to SMEI except for myoclonic seizures. We reported this group of epilepsy as intractable childhood epilepsy with GTC (ICEGTC) [Watanabe, M., Fujiwara, T., Yagi, K., Seino, M., Higashi, T., 1989b. Intractable childhood epilepsy with generalized tonic-clonic seizures. J. Jpn. Epil. Soc. 7, 96-105 (in Japanese); Fujiwara, T., Watanabe, M., Takahashi, Y., Higashi, T., Yagi, K., Seino, M., 1992. Long-term course of childhood epilepsy with intractable grand mal seizures. Jpn. J. Psychiatr. Neurol. 46, 297-302]. Recently, mutations of the neuronal voltage-gated sodium channel alphasubunit type 1 gene (SCN1A) have been found in SMEI [Claes, L., Del-Favero, J., Ceulemans, B., Lagae, L., Van Broeckhoven, C., De Jonghe, P., 2001, De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am. J. Hum. Genet. 68, 327-1332]. Mutations in SCN1A are found in both SMEI and ICEGTC at high rates of 70-81%. The loci of the mutations seen in ICEGTC are quite similar to those found in SMEI, suggesting a genotypic continuity between these entities. The clinical spectrum of epilepsies harboring SCN1A mutations may be consisted of various phenotypes with GEFS+ on the mildest end and SMEI on the severest end of the spectrum.
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorder, 886 Urushiyama, Shizuoka 420-8688, Japan. fuji@szec.hosp.go.jp
authors.forename: Tateki
authors.initials: T
authors.lastname: Fujiwara
mesh_terms: D017668:Age of Onset; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D004830:Epilepsy, Tonic-Clonic / Q000235:genetics*; D006801:Humans; D007223:Infant; D009154:Mutation; D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins / Q000235:genetics*; D010641:Phenotype; D015222:Sodium Channels / Q000235:genetics*; D013577:Syndrome; D014430:Twins, Monozygotic / Q000235:genetics*
chemical_list: D062550:NAV1.1 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; C568242:SCN1A protein, human; D015222:Sodium Channels