PRRT2 benign familial infantile seizures (BFIS) with atypical evolution to encephalopathy related to status epilepticus during sleep (ESES)

Alberto Cossu, Joana L. Santos, Giulia Galati, Marina Nikanorova, Paola Costa, Yuan Mang, Asli Silahtaroglu, Guido Rubboli, Niels Tommerup, Bernardo Dalla Bernardina, Rikke S. Møller, Gaetano Cantalupo, Elena Gardella*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

2 Citations (Scopus)

Abstract

Purpose : Heterozygous variants in PRRT2 are mostly associated with benign phenotypes, being the major genetic cause of benign familial infantile seizures (BFIS), as well as in paroxysmal disorders. We report two children from unrelated families with BFIS that evolved to encephalopathy related to status epilepticus during sleep (ESES). Methods and results: Two probands presented with focal motor seizures at 3 months of age, with a limited course. Both children presented, at around 5 years of age, with centro-temporal interictal epileptiform discharges with a source in the frontal operculum, markedly activated by sleep, and associated with stagnation on neuropsychological development. Whole-exome sequencing and co-segregation analysis revealed a frameshift mutation c.649dupC in the proline-rich transmembrane protein 2 (PRRT2) in both probands and all affected family members. Conclusion: The mechanism leading to epilepsy and the phenotypic variability of PRRT2 variants remain poorly understood. However, its wide cortical and subcortical expression, in particular in the thalamus, could partially explain both the focal EEG pattern and the evolution to ESES. No variants in the PRRT2 gene have been previously reported in patients with ESES. Due to the rarity of this phenotype, other possible causative cofactors are likely contributing to the more severe course of BFIS in our probands.

Original languageEnglish
JournalNeurological Sciences
Volume44
Issue number6
Pages (from-to)2173-2176
Number of pages4
ISSN1590-1874
DOIs
Publication statusPublished - 2023

Bibliographical note

Publisher Copyright:
© 2023, Fondazione Società Italiana di Neurologia.

Keywords

  • BFIS
  • CSWS
  • ESES
  • Proline-rich transmembrane protein 2 mutation

Cite this