Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies

Research output: Contribution to journalArticleResearchpeer-review

Abstract

Purpose: Although the genetic and clinical aspects of epilepsy with myoclonic-atonic seizures (MAE) and early onset absence epilepsy (EOAE) have been investigated thoroughly, other early childhood-onset generalized epilepsies that share clinical features with MAE and EOAE have not been characterized. In this study, we aimed to delineate the genetic and phenotypic spectrum of early childhood-onset generalized epilepsies, including MAE and EOAE. Methods: We recruited 61 patients diagnosed with MAE, EOAE, genetic epilepsy with febrile seizure plus (GEFS+) and unclassified generalized epilepsies that shared seizure onset age and seizure types. Genetic causes were investigated through targeted gene panel testing, whole exome sequencing, chromosomal microarray, and single-gene Sanger sequencing. Results: We classified 11 patients with MAE, 20 with EOAE, 9 with GEFS + spectrum. Epilepsy syndrome was not specified in the remaining 21 patients. The clinical features were comparable across groups. Nevertheless, patients with EOAE tended to show better developmental and seizure outcomes. A total of 23 pathogenic sequences and copy number variants from 12 genes were identified (23/61, 37.7%). Genetic etiologies were confirmed in 36.4% (4/11) of the MAE group, 45% (9/20) of the EOAE group, 22.2% (2/9) of the GEFS + spectrum, and 38.1% (8/21) of the unclassified group. The most frequently identified genes with pathogenic variants were SLC6A1 (7 patients), SLC2A1 (4 patients), and SYNGAP1 (4 patients). Conclusion: Early childhood-onset generalized epilepsy appeared to be characterized by an overlapping genetic and phenotypic spectrum. SLC6A1 and SLC2A1 appeared to be important genetic causes of early childhood-onset generalized epilepsy.

Original languageEnglish
Pages (from-to)222-228
Number of pages7
JournalSeizure
Volume71
DOIs
StatePublished - 1 Oct 2019

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Generalized Epilepsy
Absence Epilepsy
Seizures
Genes
Epilepsy
Myoclonic Epilepsy
Exome
Febrile Seizures
Age of Onset

Keywords

  • Early onset absence epilepsy
  • Epilepsy with myoclonic-atonic seizures
  • Genetic testing

Cite this

@article{9420b5b5fe844e888fbb731b32e39702,
title = "Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies",
abstract = "Purpose: Although the genetic and clinical aspects of epilepsy with myoclonic-atonic seizures (MAE) and early onset absence epilepsy (EOAE) have been investigated thoroughly, other early childhood-onset generalized epilepsies that share clinical features with MAE and EOAE have not been characterized. In this study, we aimed to delineate the genetic and phenotypic spectrum of early childhood-onset generalized epilepsies, including MAE and EOAE. Methods: We recruited 61 patients diagnosed with MAE, EOAE, genetic epilepsy with febrile seizure plus (GEFS+) and unclassified generalized epilepsies that shared seizure onset age and seizure types. Genetic causes were investigated through targeted gene panel testing, whole exome sequencing, chromosomal microarray, and single-gene Sanger sequencing. Results: We classified 11 patients with MAE, 20 with EOAE, 9 with GEFS + spectrum. Epilepsy syndrome was not specified in the remaining 21 patients. The clinical features were comparable across groups. Nevertheless, patients with EOAE tended to show better developmental and seizure outcomes. A total of 23 pathogenic sequences and copy number variants from 12 genes were identified (23/61, 37.7{\%}). Genetic etiologies were confirmed in 36.4{\%} (4/11) of the MAE group, 45{\%} (9/20) of the EOAE group, 22.2{\%} (2/9) of the GEFS + spectrum, and 38.1{\%} (8/21) of the unclassified group. The most frequently identified genes with pathogenic variants were SLC6A1 (7 patients), SLC2A1 (4 patients), and SYNGAP1 (4 patients). Conclusion: Early childhood-onset generalized epilepsy appeared to be characterized by an overlapping genetic and phenotypic spectrum. SLC6A1 and SLC2A1 appeared to be important genetic causes of early childhood-onset generalized epilepsy.",
keywords = "Early onset absence epilepsy, Epilepsy with myoclonic-atonic seizures, Genetic testing",
author = "Kim, {Soo Yeon} and Jang, {Se Song} and Jong-Il Kim and Hunmin Kim and Hee Hwang and Jieun Choi and Chae, {Jong Hee} and Kijoong Kim and Lim, {Byung Chan}",
year = "2019",
month = "10",
day = "1",
doi = "10.1016/j.seizure.2019.07.024",
language = "English",
volume = "71",
pages = "222--228",
journal = "Seizure",
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Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies. / Kim, Soo Yeon; Jang, Se Song; Kim, Jong-Il; Kim, Hunmin; Hwang, Hee; Choi, Jieun; Chae, Jong Hee; Kim, Kijoong; Lim, Byung Chan.

In: Seizure, Vol. 71, 01.10.2019, p. 222-228.

Research output: Contribution to journalArticleResearchpeer-review

TY - JOUR

T1 - Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies

AU - Kim, Soo Yeon

AU - Jang, Se Song

AU - Kim, Jong-Il

AU - Kim, Hunmin

AU - Hwang, Hee

AU - Choi, Jieun

AU - Chae, Jong Hee

AU - Kim, Kijoong

AU - Lim, Byung Chan

PY - 2019/10/1

Y1 - 2019/10/1

N2 - Purpose: Although the genetic and clinical aspects of epilepsy with myoclonic-atonic seizures (MAE) and early onset absence epilepsy (EOAE) have been investigated thoroughly, other early childhood-onset generalized epilepsies that share clinical features with MAE and EOAE have not been characterized. In this study, we aimed to delineate the genetic and phenotypic spectrum of early childhood-onset generalized epilepsies, including MAE and EOAE. Methods: We recruited 61 patients diagnosed with MAE, EOAE, genetic epilepsy with febrile seizure plus (GEFS+) and unclassified generalized epilepsies that shared seizure onset age and seizure types. Genetic causes were investigated through targeted gene panel testing, whole exome sequencing, chromosomal microarray, and single-gene Sanger sequencing. Results: We classified 11 patients with MAE, 20 with EOAE, 9 with GEFS + spectrum. Epilepsy syndrome was not specified in the remaining 21 patients. The clinical features were comparable across groups. Nevertheless, patients with EOAE tended to show better developmental and seizure outcomes. A total of 23 pathogenic sequences and copy number variants from 12 genes were identified (23/61, 37.7%). Genetic etiologies were confirmed in 36.4% (4/11) of the MAE group, 45% (9/20) of the EOAE group, 22.2% (2/9) of the GEFS + spectrum, and 38.1% (8/21) of the unclassified group. The most frequently identified genes with pathogenic variants were SLC6A1 (7 patients), SLC2A1 (4 patients), and SYNGAP1 (4 patients). Conclusion: Early childhood-onset generalized epilepsy appeared to be characterized by an overlapping genetic and phenotypic spectrum. SLC6A1 and SLC2A1 appeared to be important genetic causes of early childhood-onset generalized epilepsy.

AB - Purpose: Although the genetic and clinical aspects of epilepsy with myoclonic-atonic seizures (MAE) and early onset absence epilepsy (EOAE) have been investigated thoroughly, other early childhood-onset generalized epilepsies that share clinical features with MAE and EOAE have not been characterized. In this study, we aimed to delineate the genetic and phenotypic spectrum of early childhood-onset generalized epilepsies, including MAE and EOAE. Methods: We recruited 61 patients diagnosed with MAE, EOAE, genetic epilepsy with febrile seizure plus (GEFS+) and unclassified generalized epilepsies that shared seizure onset age and seizure types. Genetic causes were investigated through targeted gene panel testing, whole exome sequencing, chromosomal microarray, and single-gene Sanger sequencing. Results: We classified 11 patients with MAE, 20 with EOAE, 9 with GEFS + spectrum. Epilepsy syndrome was not specified in the remaining 21 patients. The clinical features were comparable across groups. Nevertheless, patients with EOAE tended to show better developmental and seizure outcomes. A total of 23 pathogenic sequences and copy number variants from 12 genes were identified (23/61, 37.7%). Genetic etiologies were confirmed in 36.4% (4/11) of the MAE group, 45% (9/20) of the EOAE group, 22.2% (2/9) of the GEFS + spectrum, and 38.1% (8/21) of the unclassified group. The most frequently identified genes with pathogenic variants were SLC6A1 (7 patients), SLC2A1 (4 patients), and SYNGAP1 (4 patients). Conclusion: Early childhood-onset generalized epilepsy appeared to be characterized by an overlapping genetic and phenotypic spectrum. SLC6A1 and SLC2A1 appeared to be important genetic causes of early childhood-onset generalized epilepsy.

KW - Early onset absence epilepsy

KW - Epilepsy with myoclonic-atonic seizures

KW - Genetic testing

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U2 - 10.1016/j.seizure.2019.07.024

DO - 10.1016/j.seizure.2019.07.024

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EP - 228

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