Ann Child Neurol.  2024 Apr;32(2):67-82. 10.26815/acn.2023.00367.

The Genetic Facets of Dravet Syndrome: Recent Insights

Affiliations
  • 1Laboratory of Biomedical and Translational Research, Faculty of Medicine and Pharmacy and Dental Medicine, Sidi Mohamed Ben Abdellah University, Fez, Morocco
  • 2Unit of Medical Genetics and Oncogenetics, University Hospital Hassan II, Fez, Morocco
  • 3Engineering Science and Technology Doctoral Study Center, Faculty of Sciences and Technologies, Sidi Mohamed Ben Abdellah University, Fez, Morocco
  • 4Laboratory of Biotechnology, Environment, Agri-Food, and Health (LBEAH), Faculty of Sciences Dhar El Mahraz, Sidi Mohamed Ben Abdellah University, Fez, Morocco
  • 5Faculty of Medicine and Pharmacy, University Mohammed V, Rabat, Morocco
  • 6Department of Pediatrics CHU Hassan II, Fez, Morocco

Abstract

Dravet syndrome (DS), previously known as severe myoclonic epilepsy of infancy, is a severe epileptic syndrome affecting children, with an incidence of 1/22,000 to 1/49,900 live births annually. Characterized by resistant and prolonged seizures, it often leads to intellectual impairment, with males being twice as susceptible as females. Its clinical features include recurrent seizures triggered by fever initially, but later occurring spontaneously, developmental delays, behavioral issues, and movement disorders. Sodium voltage-gated channel alpha subunit 1 (SCN1A) mutations, observed in about 90% of cases, are usually de novo, while mutations in other genes, such as protocadherin 19 (PCDH19), gamma-aminobutyric acid type A receptor subunit gamma 2 (GABRG2), and sodium voltage-gated channel alpha subunit 2 (SCN2A), can also contribute to the condition. Next-generation sequencing aids in identifying these genetic abnormalities. First-line treatments include anticonvulsant drugs such as valproate, clobazam, stiripentol, topiramate, and bromide. Second-line treatments for drug-resistant DS include stiripentol, fenfluramine, and cannabidiol. This literature review provides a comprehensive update on the genetic underpinnings of DS, highlighting SCN1A's predominant role and the emerging significance of other genes. Moreover, it emphasizes novel therapeutic approaches for drug-resistant forms, showcasing the efficacy of newer drugs such as stiripentol, fenfluramine, and cannabidiol. This synthesis contributes to our understanding of the genetic landscape of DS and informs clinicians about evolving treatment strategies for enhanced patient care.

Keyword

Epilepsies, myoclonic; Genetics; Mutation; Genes
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