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Journal of Pediatric Neurology 2023; 21(03): 168-172
DOI: 10.1055/s-0041-1727268
Review Article

SCN1B Gene: A Close Relative to SCN1A

Elisa Pasquetti
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Manuela Lo Bianco
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Federica Sullo
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Francesca Patanè
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Laura Sciuto
1   Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy
,
Agata Polizzi
2   Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy
,
Andrea D. Praticò
3   Unit of Rare Diseases of the Nervous System in Childhood, Department of Clinical and Experimental Medicine, Section of Pediatrics and Child Neuropsychiatry, University of Catania, Catania, Italy
,
Antonio Zanghì
4   Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy
,
Raffaele Falsaperla
5   Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
6   Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy
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Abstract

One of the first reported genes associated with epilepsy was SCN1B, which encodes for β-subunit of voltage-gated sodium channel of excitable cells and it is critical for neuronal function in both central and peripheral nervous system. β-subunits modulate the expression levels and functional properties of sodium channels and though their immunoglobulin domains may mediate interactions between channels and other proteins. Traditionally, SCN1B mutations were associated with generalized epilepsy with febrile seizures plus, a familial epilepsy syndrome characterized by heterogeneous phenotypes including febrile seizures (FS), febrile seizures plus (FS + ), mild generalized epilepsies, and severe epileptic encephalopathies. Throughout the years, SCN1B mutations have been also associated with Dravet syndrome and, more recently, with developmental and epileptic encephalopathies, expanding the spectrum associated with this gene mutations to more severe phenotypes.

Keywords

SCN1B - SCN1 - epilepsy - febrile seizures - GEFS+


Publication History

Received: 06 September 2020

Accepted: 25 February 2021

Article published online:
13 April 2021

© 2021. Thieme. All rights reserved.

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  • References

  • 1 Wallace RH, Wang DW, 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 (04) 366-370
    CrossrefPubMedGoogle Scholar
  • 2 Myers KA, Scheffer IE, Berkovic SF. ILAE Genetics Commission. Genetic literacy series: genetic epilepsy with febrile seizures plus. Epileptic Disord 2018; 20 (04) 232-238
    CrossrefPubMedGoogle Scholar
  • 3 Meadows LS, Malhotra J, Loukas A. et al. Functional and biochemical analysis of a sodium channel beta1 subunit mutation responsible for generalized epilepsy with febrile seizures plus type 1. J Neurosci 2002; 22 (24) 10699-10709
    CrossrefPubMedGoogle Scholar
  • 4 Ruggieri M, Rizzo R, Pavone P, Baieli S, Sorge G, Happle R. Temporal triangular alopecia in association with mental retardation and epilepsy in a mother and daughter. Arch Dermatol 2000; 136 (03) 426-427
    CrossrefPubMedGoogle Scholar
  • 5 Ruggieri M, Iannetti P, Clementi M. et al. Neurofibromatosis type 1 and infantile spasms. Childs Nerv Syst 2009; 25 (02) 211-216
    CrossrefPubMedGoogle Scholar
  • 6 Patino GA, Claes LR, Lopez-Santiago LF. et al. A functional null mutation of SCN1B in a patient with Dravet syndrome. J Neurosci 2009; 29 (34) 10764-10778
    CrossrefPubMedGoogle Scholar
  • 7 Ogiwara I, Nakayama T, Yamagata T. et al. A homozygous mutation of voltage-gated sodium channel β(I) gene SCN1B in a patient with Dravet syndrome. Epilepsia 2012; 53 (12) e200-e203
    CrossrefPubMedGoogle Scholar
  • 8 Praticò AD, Falsaperla R, Ruggieri M, Corsello G, Pavone P. Prognostic challenges of SCN1A genetic mutations: report on two children with mild features. J Pediatr Neurol 2016; 14: 82-88
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Connolly MB. Dravet syndrome: diagnosis and long-term course. Can J Neurol Sci 2016; 43 (Suppl 3): S3-S8
    CrossrefPubMedGoogle Scholar
  • 10 Pavone P, Briuglia S, Falsaperla R. et al. Wide spectrum of congenital anomalies including choanal atresia, malformed extremities, and brain and spinal malformations in a girl with a de novo 5.6-Mb deletion of 13q12.11-13q12.13. Am J Med Genet A 2014; 164A (07) 1734-1743
    CrossrefPubMedGoogle Scholar
  • 11 Kiernan MC, Krishnan AV, Lin CS, Burke D, Berkovic SF. Mutation in the Na+ channel subunit SCN1B produces paradoxical changes in peripheral nerve excitability. Brain 2005; 128 (Pt 8): 1841-1846
    CrossrefPubMedGoogle Scholar
  • 12 Isom LL, De Jongh KS, Patton DE. et al. Primary structure and functional expression of the beta 1 subunit of the rat brain sodium channel. Science 1992; 256 (5058): 839-842
    CrossrefPubMedGoogle Scholar
  • 13 Ruggieri M, Polizzi A, Pavone L, Musumeci S. Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998; 101 (1 Pt 1): 112-119
    CrossrefPubMedGoogle Scholar
  • 14 Salpietro V, Polizzi A, Di Rosa G. et al. Adrenal disorders and the paediatric brain: pathophysiological considerations and clinical implications. Int J Endocrinol 2014; 2014: 282489
    CrossrefPubMedGoogle Scholar
  • 15 Chen C, Westenbroek RE, Xu X. et al. Mice lacking sodium channel beta1 subunits display defects in neuronal excitability, sodium channel expression, and nodal architecture. J Neurosci 2004; 24 (16) 4030-4042
    CrossrefPubMedGoogle Scholar
  • 16 Salpietro V, Mankad K, Kinali M. et al. Pediatric idiopathic intracranial hypertension and the underlying endocrine-metabolic dysfunction: a pilot study. J Pediatr Endocrinol Metab 2014; 27 (1-2): 107-115
    CrossrefPubMedGoogle Scholar
  • 17 Bouza AA, Isom LL. Voltage-gated sodium channel β subunits and their related diseases. Handb Exp Pharmacol 2018; 246: 423-450
    CrossrefPubMedGoogle Scholar
  • 18 Pavone P, Praticò AD, Vitaliti G. et al. Hydranencephaly: cerebral spinal fluid instead of cerebral mantles. Ital J Pediatr 2014; 40: 79
    CrossrefPubMedGoogle Scholar
  • 19 Ruggieri M, Praticò AD, Serra A. et al. Childhood neurofibromatosis type 2 (NF2) and related disorders: from bench to bedside and biologically targeted therapies. Acta Otorhinolaryngol Ital 2016; 36 (05) 345-367
    PubMedGoogle Scholar
  • 20 Ruggieri M, Milone P, Pavone P. et al. Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet A 2012; 158A (11) 2870-2880
    CrossrefPubMedGoogle Scholar
  • 21 Ruggieri M, Iannetti P, Pavone L. Delineation of a newly recognized neurocutaneous malformation syndrome with “cutis tricolor”. Am J Med Genet A 2003; 120A (01) 110-116
    CrossrefPubMedGoogle Scholar
  • 22 Wallace RH, Scheffer IE, Parasivam G. et al. Generalized epilepsy with febrile seizures plus: mutation of the sodium channel subunit SCN1B. Neurology 2002; 58 (09) 1426-1429
    CrossrefPubMedGoogle Scholar
  • 23 Falsaperla R, Perciavalle V, Pavone P. et al. Unilateral eye blinking arising from the ictal ipsilateral occipital area. Clin EEG Neurosci 2016; 47 (03) 243-246
    CrossrefPubMedGoogle Scholar
  • 24 Scheffer IE, Harkin LA, Grinton BE. et al. Temporal lobe epilepsy and GEFS+ phenotypes associated with SCN1B mutations. Brain 2007; 130 (Pt 1): 100-109
    CrossrefPubMedGoogle Scholar
  • 25 Fendri-Kriaa N, Kammoun F, Salem IH. et al. New mutation c.374C>T and a putative disease-associated haplotype within SCN1B gene in Tunisian families with febrile seizures. Eur J Neurol 2011; 18 (05) 695-702
    CrossrefPubMedGoogle Scholar
  • 26 Miao P, Feng J, Guo Y. et al. Genotype and phenotype analysis using an epilepsy-associated gene panel in Chinese pediatric epilepsy patients. Clin Genet 2018; 94 (06) 512-520
    CrossrefPubMedGoogle Scholar
  • 27 Audenaert D, Claes L, Ceulemans B, Löfgren A, Van Broeckhoven C, De Jonghe P. A deletion in SCN1B is associated with febrile seizures and early-onset absence epilepsy. Neurology 2003; 61 (06) 854-856
    CrossrefPubMedGoogle Scholar
  • 28 Incorpora G, Pavone P, Castellano-Chiodo D, Praticò AD, Ruggieri M, Pavone L. Gelastic seizures due to hypothalamic hamartoma: rapid resolution after endoscopic tumor disconnection. Neurocase 2013; 19 (05) 458-461
    CrossrefPubMedGoogle Scholar
  • 29 Myers KA, Shevell MI, Sébire G. Sudden unexpected death in GEFS+ families with sodium channel pathogenic variants. Epilepsy Res 2019; 150: 66-69
    CrossrefPubMedGoogle Scholar
  • 30 Lionetti E, Leonardi S, Franzonello C, Mancardi M, Ruggieri M, Catassi C. Gluten psychosis: confirmation of a new clinical entity. Nutrients 2015; 7 (07) 5532-5539
    CrossrefPubMedGoogle Scholar
  • 31 Darras N, Ha TK, Rego S. et al. Developmental and epileptic encephalopathy in two siblings with a novel, homozygous missense variant in SCN1B. Am J Med Genet A 2019; 179 (11) 2190-2195
    CrossrefPubMedGoogle Scholar
  • 32 Aeby A, Sculier C, Bouza AA. et al. SCN1B-linked early infantile developmental and epileptic encephalopathy. Ann Clin Transl Neurol 2019; 6 (12) 2354-2367
    CrossrefPubMedGoogle Scholar
  • 33 Pratico AD, Longo L, Mansueto S. et al. Off-label use of drugs and adverse drug reactions in pediatric units: a prospective, multicenter study. Curr Drug Saf 2018; 13 (03) 200-207
    CrossrefPubMedGoogle Scholar
  • 34 Pratico AD, Ruggieri M, Falsaperla R, Pavone P. A probable topiramate-induced limbs paraesthesia and rigid fingers flexion. Curr Drug Saf 2018; 13 (02) 131-136
    CrossrefPubMedGoogle Scholar
  • 35 Falsaperla R, D'Angelo G, Praticò AD. et al. Ketogenic diet for infants with epilepsy: a literature review. Epilepsy Behav 2020; 112: 107361
    CrossrefPubMedGoogle Scholar
  • 36 Dang LT, Quinonez SC, Becka BR, Isom LL, Joshi SM. Dramatic improvement in seizures with phenytoin treatment in an individual with refractory epilepsy and a SCN1B variant. Pediatr Neurol 2020; 108: 121-122
    CrossrefPubMedGoogle Scholar
  • 37 Sorge G, Ruggieri M, Polizzi A, Scuderi A, Di Pietro M. SHORT syndrome: a new case with probable autosomal dominant inheritance. Am J Med Genet 1996; 61 (02) 178-181
    CrossrefPubMedGoogle Scholar
  • 38 Pavone P, Praticò AD, Ruggieri M. et al. Acquired peripheral neuropathy: a report on 20 children. Int J Immunopathol Pharmacol 2012; 25 (02) 513-517
    CrossrefPubMedGoogle Scholar
  • 39 Pavone P, Falsaperla R, Ruggieri M, Praticò AD, Pavone L. West syndrome treatment: new roads for an old syndrome. Front Neurol 2013; 4: 113
    CrossrefPubMedGoogle Scholar
  • 40 Ruggieri M, Pavone V, De Luca D, Franzò A, Tiné A, Pavone L. Congenital bone malformations in patients with neurofibromatosis type 1 (Nf1). J Pediatr Orthop 1999; 19 (03) 301-305
    CrossrefPubMedGoogle Scholar
  • 41 Praticò AD, Polizzi A, Salafia R. et al. Megalencephaly capillary malformation syndrome. J Pediatr Neurol 2018; 16: 328-337
    Article in Thieme ConnectPubMedGoogle Scholar