Dissecting the phenotypic and genetic spectrum of early childhood-onset generalized epilepsies.
Seizure
; 71: 222-228, 2019 Oct.
Article
en En
| MEDLINE
| ID: mdl-31401500
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 GEFSâ¯+â¯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 GEFSâ¯+â¯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.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Epilepsia Generalizada
/
Convulsiones Febriles
Tipo de estudio:
Prognostic_studies
Límite:
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
Idioma:
En
Revista:
Seizure
Asunto de la revista:
NEUROLOGIA
Año:
2019
Tipo del documento:
Article