Genetic and clinical features of SCN8A developmental and epileptic encephalopathy

Hyo Jeong Kim, Donghwa Yang, Se Hee Kim, Borahm Kim, Heung Dong Kim, Joon Soo Lee, Jong Rak Choi, Seung Tae Lee, Hoon Chul Kang

Research output: Contribution to journalArticle

Abstract

Objective: We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Methods: Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. Results: The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. Conclusion: SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.

Original languageEnglish
Article number106222
JournalEpilepsy Research
Volume158
DOIs
Publication statusPublished - 2019 Dec

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Brain Diseases
Sodium Channel Blockers
Seizures
Status Epilepticus
Spasm
Mutation
Infantile Spasms
Microcephaly
Muscle Hypotonia
Partial Epilepsy
Missense Mutation
Ataxia
Electroencephalography
Epilepsy
Proteins
Phenotype

All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

Cite this

Kim, Hyo Jeong ; Yang, Donghwa ; Kim, Se Hee ; Kim, Borahm ; Kim, Heung Dong ; Lee, Joon Soo ; Choi, Jong Rak ; Lee, Seung Tae ; Kang, Hoon Chul. / Genetic and clinical features of SCN8A developmental and epileptic encephalopathy. In: Epilepsy Research. 2019 ; Vol. 158.
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abstract = "Objective: We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Methods: Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. Results: The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. Conclusion: SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.",
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Genetic and clinical features of SCN8A developmental and epileptic encephalopathy. / Kim, Hyo Jeong; Yang, Donghwa; Kim, Se Hee; Kim, Borahm; Kim, Heung Dong; Lee, Joon Soo; Choi, Jong Rak; Lee, Seung Tae; Kang, Hoon Chul.

In: Epilepsy Research, Vol. 158, 106222, 12.2019.

Research output: Contribution to journalArticle

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AU - Kim, Hyo Jeong

AU - Yang, Donghwa

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AU - Kim, Heung Dong

AU - Lee, Joon Soo

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AU - Lee, Seung Tae

AU - Kang, Hoon Chul

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N2 - Objective: We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Methods: Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. Results: The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. Conclusion: SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.

AB - Objective: We aim to delineate the genetic and clinical features of SCN8A developmental and epileptic encephalopathy. Methods: Nine patients with SCN8A developmental and epileptic encephalopathy were included in this study. Genetic and clinical features and effectiveness of sodium channel blockers were assessed in patients who were confirmed with SCN8A mutations. Results: The onset of seizures ranged from the neonatal period to 18 months of age. Seizure types were diverse and predominantly involved focal seizures or spasms. The most common initial epilepsy syndrome was West syndrome in four patients, followed by neonatal-onset focal seizures in three patients and unclassified focal epilepsy in two patients. Electroencephalograms (EEGs) showed slow and disorganized background and epileptiform abnormalities with occipital predominance. Six patients presented intractable seizures including one patient with recurrent nonconvulsive status epilepticus. Sodium channel blockers were effective in seven patients among eight patients given them. All patients showed developmental delay or regression. Severe hypotonia or ataxia was also presented in some patients. Microcephaly was also characteristic. De novo missense mutations in SCN8A were found in the inactivation gate, C-terminal, loop 2, and transmembrane segments (S1, 4, 5, and 6). There was no correlation between the location of the mutation in the protein and phenotype or response to sodium channel blockers. Conclusion: SCN8A developmental and epileptic encephalopathy presents intractable seizures including spasms, focal seizures, neonatal status epilepticus, and nonconvulsive status epilepticus. Sodium channel blockers were effective irrelevant to the location of the mutation in the protein.

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