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Journal of Pediatric Neurology 2016; 14(02): 082-088
DOI: 10.1055/s-0036-1583274
Case Report
Georg Thieme Verlag KG Stuttgart · New York

Prognostic Challenges of SCN1A Genetic Mutations: Report on Two Children with Mild Features

Andrea D. Praticò
1   Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
2   Department of Clinical and Molecular Biomedicine, University of Catania, Catania, Italy
,
Raffaele Falsaperla
3   University-Hospital “Policlinico-Vittorio Emanuele,” University of Catania, Catania, Italy
,
Martino Ruggieri
1   Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Giovanni Corsello
4   Department of Sciences for Health Promotion and Mother and Child Care, Pediatric Unit, University of Palermo, Palermo, Italy
,
Piero Pavone
3   University-Hospital “Policlinico-Vittorio Emanuele,” University of Catania, Catania, Italy
› Institutsangaben
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Publikationsverlauf

04. März 2015

22. Mai 2015

Publikationsdatum:
28. April 2016 (online)

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Abstract

Mutations in the gene encoding the α-1 subunit of the voltage-gated sodium channel (SCN1A) are associated with variable but usually severe clinical course, both for the epileptic seizures and the cognitive impairment. The purpose of the present study was to retrospectively review two patients affected by seizures and two different types of SCN1A gene mutations (microdeletion and point mutation). The children (a 4-year-old girl and a 3-year-old boy) were affected by generalized tonic–clonic seizures and myoclonic jerks plus unilateral seizures, respectively. Genetic analyses showed, in the girl, the presence of a 4 MB deletion involving SCN1A and four other genes, and a point mutation in the boy. Both the patients showed a mild clinical course, with a good pharmacological control of the crises and sufficient scholastic performances. At present, the role of the combination of SCN1A mutations and the related clinical manifestations is not very clear. Prognostic counseling is particularly challenging given that, in many cases, the clinical course of these patients is independent of the genotype and its severity is difficult to predict.

Keywords

Dravet syndrome - SCN1A genetic mutations - epileptic encephalopathy - Dravet syndrome spectrum
 

  • References

  • 1 Dravet C. Les epilepsies graves de l'enfant. Vie Med 1978; 8: 543-548
    PubMedGoogle Scholar
  • 2 Berg AT, Berkovic SF, Brodie MJ , 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) 676-685
    CrossrefPubMedGoogle Scholar
  • 3 Harkin LA, McMahon JM, Iona X , et al; Infantile Epileptic Encephalopathy Referral Consortium. The spectrum of SCN1A-related infantile epileptic encephalopathies. Brain 2007; 130 (Pt 3): 843-852
    CrossrefPubMedGoogle Scholar
  • 4 Oguni H, Hayashi K, Osawa M , et al. Severe myoclonic epilepsy in infancy: clinical analysis and relation to SCN1A mutations in a Japanese cohort. Adv Neurol 2005; 95: 103-117
    PubMedGoogle Scholar
  • 5 Claes L, Del-Favero J, Ceulemans B, Lagae L, Van Broeckhoven C, De Jonghe P. De novo mutations in the sodium-channel gene SCN1A cause severe myoclonic epilepsy of infancy. Am J Hum Genet 2001; 68 (6) 1327-1332
    CrossrefPubMedGoogle Scholar
  • 6 Depienne C, Trouillard O, Saint-Martin C , et al. Spectrum of SCN1A gene mutations associated with Dravet syndrome: analysis of 333 patients. J Med Genet 2009; 46 (3) 183-191
    PubMedGoogle Scholar
  • 7 Carvill GL, Weckhuysen S, McMahon JM , et al. GABRA1 and STXBP1: novel genetic causes of Dravet syndrome. Neurology 2014; 82 (14) 1245-1253
    CrossrefPubMedGoogle Scholar
  • 8 Scheffer IE, Turner SJ, Dibbens LM , et al. Epilepsy and mental retardation limited to females: an under-recognized disorder. Brain 2008; 131 (Pt 4): 918-927
    CrossrefPubMedGoogle Scholar
  • 9 Ogiwara I, Miyamoto H, Morita N , et al. Nav1.1 localizes to axons of parvalbumin-positive inhibitory interneurons: a circuit basis for epileptic seizures in mice carrying an Scn1a gene mutation. J Neurosci 2007; 27 (22) 5903-5914
    CrossrefPubMedGoogle Scholar
  • 10 Yu FH, Mantegazza M, Westenbroek RE , et al. Reduced sodium current in GABAergic interneurons in a mouse model of severe myoclonic epilepsy in infancy. Nat Neurosci 2006; 9 (9) 1142-1149
    CrossrefPubMedGoogle Scholar
  • 11 Brunklaus A, Zuberi SM. Dravet syndrome—from epileptic encephalopathy to channelopathy. Epilepsia 2014; 55 (7) 979-984
    CrossrefPubMedGoogle Scholar
  • 12 Akiyama M, Kobayashi K, Ohtsuka Y. Dravet syndrome: a genetic epileptic disorder. Acta Med Okayama 2012; 66 (5) 369-376
    PubMedGoogle Scholar
  • 13 Dravet C, Oguni H. Dravet syndrome (severe myoclonic epilepsy in infancy). Handb Clin Neurol 2013; 111: 627-633
    PubMedGoogle Scholar
  • 14 Dravet C. The core Dravet syndrome phenotype. Epilepsia 2011; 52 (Suppl. 02) 3-9
    PubMedGoogle Scholar
  • 15 Scheffer IE, Zhang YH, Jansen FE, Dibbens L. Dravet syndrome or genetic (generalized) epilepsy with febrile seizures plus?. Brain Dev 2009; 31 (5) 394-400
    CrossrefPubMedGoogle Scholar
  • 16 Kim YO, Bellows S, McMahon JM , et al. Atypical multifocal Dravet syndrome lacks generalized seizures and may show later cognitive decline. Dev Med Child Neurol 2014; 56 (1) 85-90
    CrossrefPubMedGoogle Scholar
  • 17 Zucca C, Redaelli F, Epifanio R , et al. Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified. Arch Neurol 2008; 65 (4) 489-494
    CrossrefPubMedGoogle Scholar
  • 18 Jansen FE, Sadleir LG, Harkin LA , et al. Severe myoclonic epilepsy of infancy (Dravet syndrome): recognition and diagnosis in adults. Neurology 2006; 67 (12) 2224-2226
    CrossrefPubMedGoogle Scholar
  • 19 Fujiwara T. Clinical spectrum of mutations in SCN1A gene: severe myoclonic epilepsy in infancy and related epilepsies. Epilepsy Res 2006; 70 (Suppl. 01) S223-S230
    CrossrefPubMedGoogle Scholar
  • 20 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 (Pt 3): 531-546
    CrossrefPubMedGoogle Scholar
  • 21 Fukuma G, Oguni H, Shirasaka Y , et al. Mutations of neuronal voltage-gated Na+ channel alpha 1 subunit gene SCN1A in core severe myoclonic epilepsy in infancy (SMEI) and in borderline SMEI (SMEB). Epilepsia 2004; 45 (2) 140-148
    CrossrefPubMedGoogle Scholar
  • 22 Madia F, Striano P, Gennaro E , et al. Cryptic chromosome deletions involving SCN1A in severe myoclonic epilepsy of infancy. Neurology 2006; 67 (7) 1230-1235
    CrossrefPubMedGoogle Scholar
  • 23 Incorpora G. Dravet syndrome. Ital J Pediatr 2009; 35 (1) 27
    CrossrefPubMedGoogle Scholar
  • 24 Yang Y, Wang Y, Li S , et al. Mutations in SCN9A, encoding a sodium channel alpha subunit, in patients with primary erythermalgia. J Med Genet 2004; 41 (3) 171-174
    CrossrefPubMedGoogle Scholar
  • 25 Cummins TR, Dib-Hajj SD, Waxman SG. Electrophysiological properties of mutant Nav1.7 sodium channels in a painful inherited neuropathy. J Neurosci 2004; 24 (38) 8232-8236
    CrossrefPubMedGoogle Scholar
  • 26 Cox JJ, Reimann F, Nicholas AK , et al. An SCN9A channelopathy causes congenital inability to experience pain. Nature 2006; 444 (7121) 894-898
    CrossrefPubMedGoogle Scholar
  • 27 Hiyama TY, Watanabe E, Ono K , et al. Na(x) channel involved in CNS sodium-level sensing. Nat Neurosci 2002; 5 (6) 511-512
    CrossrefPubMedGoogle Scholar
  • 28 Duka A, Schwartz F, Duka I , et al. A novel gene (Cmya3) induced in the heart by angiotensin II-dependent but not salt-dependent hypertension in mice. Am J Hypertens 2006; 19 (3) 275-281
    CrossrefPubMedGoogle Scholar
  • 29 Marini C, Scheffer IE, Nabbout R , et al. SCN1A duplications and deletions detected in Dravet syndrome: implications for molecular diagnosis. Epilepsia 2009; 50 (7) 1670-1678
    CrossrefPubMedGoogle Scholar
  • 30 Gennaro E, Veggiotti P, Malacarne M , et al. Familial severe myoclonic epilepsy of infancy: truncation of Nav1.1 and genetic heterogeneity. Epileptic Disord 2003; 5 (1) 21-25
    PubMedGoogle Scholar
  • 31 Depienne C, Trouillard O, Gourfinkel-An I , et al. Mechanisms for variable expressivity of inherited SCN1A mutations causing Dravet syndrome. J Med Genet 2010; 47 (6) 404-410
    CrossrefPubMedGoogle Scholar
  • 32 Xu X, Zhang Y, Sun H , et al. Early clinical features and diagnosis of Dravet syndrome in 138 Chinese patients with SCN1A mutations. Brain Dev 2014; 36 (8) 676-681
    CrossrefPubMedGoogle Scholar
  • 33 Suls A, Claeys KG, Goossens D , et al. Microdeletions involving the SCN1A gene may be common in SCN1A-mutation-negative SMEI patients. Hum Mutat 2006; 27 (9) 914-920
    CrossrefPubMedGoogle Scholar
  • 34 Wang JW, 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
    CrossrefPubMedGoogle Scholar
  • 35 Pescucci C, Caselli R, Grosso S , et al. 2q24-q31 deletion: report of a case and review of the literature. Eur J Med Genet 2007; 50 (1) 21-32
    CrossrefPubMedGoogle Scholar
  • 36 Davidsson J, Collin A, Olsson ME, Lundgren J, Soller M. Deletion of the SCN gene cluster on 2q24.4 is associated with severe epilepsy: an array-based genotype-phenotype correlation and a comprehensive review of previously published cases. Epilepsy Res 2008; 81 (1) 69-79
    CrossrefPubMedGoogle Scholar
  • 37 Takayama R, Fujiwara T, Shigematsu H , et al. Long-term course of Dravet syndrome: a study from an epilepsy center in Japan. Epilepsia 2014; 55 (4) 528-538
    CrossrefPubMedGoogle Scholar