SCN1A and Its Related Epileptic Phenotypes

Federica Sullo; Elisa Pasquetti; Francesca Patanè; Manuela Lo Bianco; Simona D. Marino; Agata Polizzi; Raffaele Falsaperla; Martino Ruggieri; Antonio Zanghì; Andrea D. Praticò

doi:10.1055/s-0041-1727260

Journal of Pediatric Neurology, Table of Contents

Journal of Pediatric Neurology 2023; 21(03): 155-167
DOI: 10.1055/s-0041-1727260

Review Article

SCN1A and Its Related Epileptic Phenotypes

Federica Sullo

¹Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

,

Elisa Pasquetti

¹Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

,

Francesca Patanè

¹Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

,

Manuela Lo Bianco

¹Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

,

Simona D. Marino

²Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Agata Polizzi

³Chair of Pediatrics, Department of Educational Sciences, University of Catania, Catania, Italy

,

Raffaele Falsaperla

²Unit of Pediatrics and Pediatric Emergency, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

⁴Unit of Neonatal Intensive Care and Neonatology, University Hospital “Policlinico Rodolico-San Marco,” Catania, Italy

,

Martino Ruggieri

¹Pediatrics Postgraduate Residency Program, Section of Pediatrics and Child Neuropsychiatry, Department of Clinical and Experimental Medicine, University of Catania, Catania, Italy

,

Antonio Zanghì

⁵Department of Medical and Surgical Sciences and Advanced Technology “G.F. Ingrassia,” University of Catania, Catania, Italy

,

Andrea D. Praticò

⁶Unit 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

› Author Affiliations

Abstract

Epilepsy is one of the most common neurological disorders, with a lifetime incidence of 1 in 26. Approximately two-thirds of epilepsy has a substantial genetic component in its etiology. As a result, simultaneous screening for mutations in multiple genes and performing whole exome sequencing (WES) are becoming very frequent in the clinical evaluation of children with epilepsy. In this setting, mutations in voltage-gated sodium channel (SCN) α-subunit genes are the most commonly identified cause of epilepsy, with sodium channel genes (i.e., SCN1A, SCN2A, SCN8A) being the most frequently identified causative genes. SCN1A mutations result in a wide spectrum of epilepsy phenotypes ranging from simple febrile seizures to Dravet syndrome, a severe epileptic encephalopathy. In case of mutation of SCN1A, it is also possible to observe behavioral alterations, such as impulsivity, inattentiveness, and distractibility, which can be framed in an attention deficit hyperactivity disorder (ADHD) like phenotype. Despite more than 1,200 SCN1A mutations being reported, it is not possible to assess a clear phenotype–genotype correlations. Treatment remains a challenge and seizure control is often partial and transitory.

Keywords

SCN1A - sodium channel - Dravet syndrome - febrile seizures - epilepsy

Full Text

References

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