Lamotrigine induced Brugada-pattern in a patient with genetic epilepsy associated with a novel variant in SCN9A

Gene. 2020 Sep 5;754:144847. doi: 10.1016/j.gene.2020.144847. Epub 2020 Jun 9.

Abstract

Background: A 30-year-old man presented with intellectual disability associated with epilepsy. The epilepsy was initially treated with sodium valproate and since he was 28 years-old with lamotrigine. With the addition of lamotrigine, a pattern of Brugada syndrome appeared on the electrocardiogram. The family history was positive for epilepsy from the motheŕs side, who had never been treated with lamotrigine.

Objective: Determine the genetic cause of the intellectual disability, epilepsy and Brugada syndrome of the patient and try to establish a possible correlation between the genetic background and the Brugada syndrome pattern under lamotrigine treatment.

Methods: A standard karyotype, array comparative genomic hybridization and two different NGS panels have done to the index case to identify the genetic causes of the intellectual disability, epilepsy and Brugada syndrome pattern.

Results: Genetic analyses in the family identified a de novo duplication of 1.3 Mb in 8p21.3 as well as two novel heterozygous rare variants in SCN9A and AKAP9 genes, both inherited from the mother.

Conclusion: We hypothesize that in this family the SCN9A variant was responsible for the epileptic syndrome. In addition, given that SCN9A is lightly expressed in the heart tissue, we postulate that this SCN9A variant, alone or in combination with AKAP9 variant, might be responsible for the Brugada pattern when challenged by lamotrigine.

Keywords: Brugada syndrome; Epilepsy; Lamotrigine; SCN9A.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Anticonvulsants / adverse effects*
  • Brugada Syndrome / chemically induced
  • Brugada Syndrome / genetics
  • Brugada Syndrome / pathology*
  • Epilepsy / drug therapy*
  • Epilepsy / genetics
  • Epilepsy / pathology
  • Gene Duplication*
  • Humans
  • Lamotrigine / adverse effects*
  • Male
  • NAV1.7 Voltage-Gated Sodium Channel / genetics*

Substances

  • Anticonvulsants
  • NAV1.7 Voltage-Gated Sodium Channel
  • SCN9A protein, human
  • Lamotrigine