SCN1A mutations in focal epilepsy with auditory features: widening the spectrum of GEFS plus

Francesca Bisulli, Laura Licchetta, Sara Baldassari, Lorenzo Muccioli, Caterina Marconi, Gaetano Cantalupo, Candace Myers, Veronica Menghi, Raffaella Minardi, Leonardo Caporali, Carla Marini, Renzo Guerrini, Heather C. Mefford, Paolo Tinuper, Tommaso Pippucci

Research output: Contribution to journalArticle

Abstract

Aims. Epilepsy with auditory features (EAF) is a focal epilepsy syndrome characterized by prominent auditory ictal manifestations. Two main genes, LGI1 and RELN, have been implicated in EAF, but the genetic aetiology remains unknown in half of families and most sporadic cases. We previously described a pathogenic SCN1A missense variant (p.Thr956Met) segregating in a large family in which the proband and her affected daughter had EAF, thus satisfying the minimum requirement for diagnosis of autosomal dominant EAF (ADEAF). However, the remaining eight affected family members had clinical manifestations typically found in families with genetic epilepsy with febrile seizures plus (GEFS+). We aimed to investigate the role/impact of SCN1A mutations in EAF. Methods. We detailed the phenotype of this family and report on SCN1A screening in a cohort of 29 familial and 52 sporadic LGI1 variant-negative EAF patients. Results. We identified two possibly pathogenic missense variants (p.Tyr790Phe and p.Thr140Ile) in sporadic patients (3.8%) showing typical EAF and no antecedent febrile seizures. Both p.Thr956Met and p.Tyr790Phe were previously described in unrelated patients with epilepsies within the GEFS+ spectrum. Conclusion. SCN1A mutations may be involved in EAF within the GEFS+ spectrum, however, the role of SCN1A in EAF without features that lead to a suspicion of underlying GEFS+ remains unclear and should be elucidated in future studies.

Original languageEnglish
Pages (from-to)185-191
Number of pages7
JournalEpileptic Disorders
Volume21
Issue number2
DOIs
Publication statusPublished - Apr 2019

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Keywords

  • ADEAF
  • ADLTE
  • GEFS plus
  • genetics
  • lateral temporal epilepsy

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

Cite this

Bisulli, F., Licchetta, L., Baldassari, S., Muccioli, L., Marconi, C., Cantalupo, G., Myers, C., Menghi, V., Minardi, R., Caporali, L., Marini, C., Guerrini, R., Mefford, H. C., Tinuper, P., & Pippucci, T. (2019). SCN1A mutations in focal epilepsy with auditory features: widening the spectrum of GEFS plus. Epileptic Disorders, 21(2), 185-191. https://doi.org/10.1684/epd.2019.1046