Early-Onset Developmental and Epileptic Encephalopathies of Infancy: An Overview of the Genetic Basis and Clinical Features

Pediatr Neurol. 2021 Mar:116:85-94. doi: 10.1016/j.pediatrneurol.2020.12.001. Epub 2020 Dec 13.


Our current knowledge of genetically determined forms of epilepsy has shortened the diagnostic pathway usually experienced by the families of infants diagnosed with early-onset developmental and epileptic encephalopathies. Genetic causes can be found in up to 80% of infants presenting with early-onset developmental and epileptic encephalopathies, often in the context of an uneventful perinatal history and with no clear underlying brain abnormalities. Although current disease-specific therapies remain limited and patient outcomes are often guarded, a genetic diagnosis may lead to early therapeutic intervention using new and/or repurposed therapies. In this review, an overview of epilepsy genetics, the indications for genetic testing in infants, the advantages and limitations of each test, and the challenges and ethical implications of genetic testing are discussed. In addition, the following causative genes associated with early-onset developmental and epileptic encephalopathies are discussed in detail: KCNT1, KCNQ2, KCNA2, SCN2A, SCN8A, STXBP1, CDKL5, PIGA, SPTAN1, and GNAO1. The epilepsy phenotypes, comorbidities, electroencephalgraphic findings, neuroimaging findings, and potential targeted therapies for each gene are reviewed.

Keywords: Developmental and epileptic encephalopathies; Early-onset epileptic encephalopathy; Epilepsy genetics; Infants; Precision medicine.

Publication types

  • Review

MeSH terms

  • Age of Onset
  • Epileptic Syndromes / genetics*
  • Epileptic Syndromes / physiopathology*
  • Genetic Testing*
  • Humans
  • Infant