Targeted gene panel sequencing in early infantile onset developmental and epileptic encephalopathy

Brain Dev. 2020 Jun;42(6):438-448. doi: 10.1016/j.braindev.2020.02.004. Epub 2020 Mar 2.


Background: Early-onset developmental and epileptic encephalopathy (DEE) is characterized by repeated seizures beginning within 3 months of birth and severe interictal epileptiform discharge, including burst suppression. This study assessed the utility of targeted gene panel sequencing in the genetic diagnosis of this disease.

Materials and methods: Targeted gene panel sequencing was performed in 150 early infantile-onset DEE patients (≤3 months of age), and we extensively reviewed their clinical characteristics, including therapeutic efficacy, according to genotype.

Results: Of the early infantile-onset DEE patients, 70 were neonatal-onset DEE and the other 80 patients began experiencing seizures from 1 to 3 months after birth. There were 11 different pathogenic or likely pathogenic variants among 34.7% (52/150) of patients with early infantile-onset DEE, in whom KCNQ2, STXBP1, CDKL5, and SCN1A were the major pathogenic variants. Among the neonatal-onset DEE patients, pathological genes were identified in 42.9% (30/70), indicating a significantly higher diagnostic yield than in 27.5% (22/80) of patients who experienced seizure onset 1 to 3 months after birth (p = 0.048). Among the neonatal-onset DEE group, variants in KCNQ2, STXBP1, and CDKL5 were detected at high frequencies, accounting for 66.7% (20/30) of the pathogenic or likely pathogenic variants found in this study.

Conclusion: Targeted gene panel sequencing demonstrated a high yield of pathogenic variants in the diagnosis of early-onset epileptic encephalopathy, especially in those with neonatal-onset DEE. Early diagnosis of early-onset epileptic encephalopathy may improve the prognosis of patients by earlier selection of appropriate treatment based on pathogenic variant.

Keywords: Developmental and epileptic encephalopathy; Early infantile onset seizure; Early onset epileptic encephalopathy; Neonatal seizure; Targeted gene panel sequencing.

MeSH terms

  • Brain Diseases / genetics*
  • Brain Diseases / metabolism
  • Child, Preschool
  • Epileptic Syndromes / genetics
  • Female
  • Genetic Predisposition to Disease / genetics
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • KCNQ2 Potassium Channel / genetics
  • Male
  • Munc18 Proteins / genetics
  • Mutation / genetics
  • NAV1.1 Voltage-Gated Sodium Channel / genetics
  • Phenotype
  • Seizures / genetics
  • Seizures / metabolism
  • Spasms, Infantile / diagnosis
  • Spasms, Infantile / genetics*
  • Spasms, Infantile / metabolism


  • KCNQ2 Potassium Channel
  • KCNQ2 protein, human
  • Munc18 Proteins
  • NAV1.1 Voltage-Gated Sodium Channel
  • SCN1A protein, human
  • STXBP1 protein, human

Supplementary concepts

  • CDKL5 deficiency disorder