SCN2A and Its Related Epileptic Phenotypes

Andrea D. Praticò; Alessandro Giallongo; Marta Arrabito; Silvia D'Amico; Maria Cristina Gauci; Giulia Lombardo; Agata Polizzi; Deb K. Pal; Raffaele Falsaperla; Martino Ruggieri

doi:10.1055/s-0041-1727097

SCN2A and Its Related Epileptic Phenotypes

Andrea D. Praticò^*, Alessandro Giallongo, Marta Arrabito, Silvia D'Amico, Maria Cristina Gauci, Giulia Lombardo, Agata Polizzi, Deb K. Pal, Raffaele Falsaperla, Martino Ruggieri

^*Corresponding author for this work

Basic and Clinical Neuroscience

Research output: Contribution to journal › Article › peer-review

10 Citations (Scopus)

Abstract

Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A -related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A -benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A -BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A -related epilepsies have not shown a clear genotype-phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no standardized treatment for SCN2A -related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

Original language	English
Journal	Journal of Pediatric Neurology
DOIs	https://doi.org/10.1055/s-0041-1727097
Publication status	Accepted/In press - 2021

Keywords

autism
benign familial neonatal seizures
epileptic encephalopathy
SCN2A
sodium channel

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10.1055/s-0041-1727097

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title = "SCN2A and Its Related Epileptic Phenotypes",

abstract = "Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A -related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A -benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A -BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A -related epilepsies have not shown a clear genotype-phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no standardized treatment for SCN2A -related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital). ",

keywords = "autism, benign familial neonatal seizures, epileptic encephalopathy, SCN2A, sodium channel",

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year = "2021",

doi = "10.1055/s-0041-1727097",

language = "English",

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AU - Praticò, Andrea D.

AU - Giallongo, Alessandro

AU - Arrabito, Marta

AU - D'Amico, Silvia

AU - Gauci, Maria Cristina

AU - Lombardo, Giulia

AU - Polizzi, Agata

AU - Pal, Deb K.

AU - Falsaperla, Raffaele

AU - Ruggieri, Martino

PY - 2021

Y1 - 2021

N2 - Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A -related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A -benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A -BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A -related epilepsies have not shown a clear genotype-phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no standardized treatment for SCN2A -related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

AB - Epilepsies due to SCN2A mutations can present with a broad range of phenotypes that are still not fully understood. Clinical characteristics of SNC2A -related epilepsy may vary from neonatal benign epilepsy to early-onset epileptic encephalopathy, including Ohtahara syndrome and West syndrome, and epileptic encephalopathies occurring at later ages (usually within the first 10 years of life). Some patient may present with intellectual disability and/or autism or movement disorders and without epilepsy. The heterogeneity of the phenotypes associated to such genetic mutations does not always allow the clinician to address his suspect on this gene. For this reason, diagnosis is usually made after a multiple gene panel examination through next generation sequencing (NGS) or after whole exome sequencing (WES) or whole genome sequencing (WGS). Subsequently, confirmation by Sanger sequencing can be obtained. Mutations in SCN2A are inherited as an autosomal dominant trait. Most individuals diagnosed with SCN2A -benign familial neonatal-infantile seizures (BFNIS) have an affected parent; however, hypothetically, a child may present SCN2A -BNFNIS as the result of a de novo pathogenic variant. Almost all individuals with SCN2A and severe epileptic encephalopathies have a de novo pathogenic variant. SNC2A -related epilepsies have not shown a clear genotype-phenotype correlation; in some cases, a same variant may lead to different presentations even within the same family and this could be due to other genetic factors or to environmental causes. There is no standardized treatment for SCN2A -related epilepsy, as it varies in relation to the clinical presentation and the phenotype of the patient, according to its own gene mutation. Treatment is based mainly on antiepileptic drugs, which include classic wide-spectrum drugs, such as valproic acid, levetiracetam, and lamotrigine. However, specific agents, which act directly modulating the sodium channels activity (phenytoin, carbamazepine, oxcarbamazepine, lamotrigine, and zonisamide), have shown positive result, as other sodium channel blockers (lidocaine and mexiletine) or even other drugs with different targets (phenobarbital).

KW - autism

KW - benign familial neonatal seizures

KW - epileptic encephalopathy

KW - SCN2A

KW - sodium channel

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DO - 10.1055/s-0041-1727097

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SN - 1304-2580

JO - Journal of Pediatric Neurology

JF - Journal of Pediatric Neurology

ER -

SCN2A and Its Related Epileptic Phenotypes

Abstract

Keywords

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