Epilepsy Genetics and Precision Medicine in Adults: A New Landscape for Developmental and Epileptic Encephalopathies

Álvaro Beltrán-Corbellini, Ángel Aledo-Serrano*, Rikke S. Møller, Eduardo Pérez-Palma, Irene García-Morales, Rafael Toledano, Antonio Gil-Nagel

*Corresponding author for this work

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Abstract

This review aims to provide an updated perspective of epilepsy genetics and precision medicine in adult patients, with special focus on developmental and epileptic encephalopathies (DEEs), covering relevant and controversial issues, such as defining candidates for genetic testing, which genetic tests to request and how to interpret them. A literature review was conducted, including findings in the discussion and recommendations. DEEs are wide and phenotypically heterogeneous electroclinical syndromes. They generally have a pediatric presentation, but patients frequently reach adulthood still undiagnosed. Identifying the etiology is essential, because there lies the key for precision medicine. Phenotypes modify according to age, and although deep phenotyping has allowed to outline certain entities, genotype-phenotype correlations are still poor, commonly leading to long-lasting diagnostic odysseys and ineffective therapies. Recent adult series show that the target patients to be identified for genetic testing are those with epilepsy and different risk factors. The clinician should take active part in the assessment of the pathogenicity of the variants detected, especially concerning variants of uncertain significance. An accurate diagnosis implies precision medicine, meaning genetic counseling, prognosis, possible future therapies, and a reduction of iatrogeny. Up to date, there are a few tens of gene mutations with additional concrete treatments, including those with restrictive/substitutive therapies, those with therapies modifying signaling pathways, and channelopathies, that are worth to be assessed in adults. Further research is needed regarding phenotyping of adult syndromes, early diagnosis, and the development of targeted therapies.

Original languageEnglish
Article number777115
JournalFrontiers in Neurology
Volume13
Number of pages12
ISSN1664-2295
DOIs
Publication statusPublished - 17. Feb 2022

Bibliographical note

Publisher Copyright:
Copyright © 2022 Beltrán-Corbellini, Aledo-Serrano, Møller, Pérez-Palma, García-Morales, Toledano and Gil-Nagel.

Keywords

  • diagnostic yield
  • genetic testing
  • intellectual disability
  • neurogenetics
  • personalized medicine
  • precision therapy
  • rare diseases
  • seizure

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