Epilepsy phenotypes across the different age-ranges in IQSEC2-related encephalopathy: An Italian multicentre retrospective cohort study

Seizure. 2024 Jul:119:119-127. doi: 10.1016/j.seizure.2024.06.002. Epub 2024 Jun 4.

Abstract

Background: Epilepsy is a hallmark of IQSEC2-related encephalopathy within a phenotypic variability ranging between early onset epileptic and developmental encephalopathy and X-linked intellectual disability with epilepsy.

Patients and methods: Data including demographic aspects, gene variants, seizure semiology and timing, EEG features, neuroimaging and response to therapy were retrospectively collected in patients with IQSEC2-related epilepsy referring to 8 Italian tertiary centres.

Results: The reported cohort included 11 patients (8 males and 3 females). Mean age at the onset of epilepsy was 3.90±2.80 years. No cases were reported in the first year of life. No specific epileptic syndromes were recognized. Predominant seizure-types in the age range 12-36 months included focal onset tonic seizures with impaired awareness, myoclonic seizures, and late onset spasms. Generalized motor seizures were predominant in patients between 3 and 6 years and between 12 and 18 years while focal motor seizures with impaired awareness were the most represented types between 6 and 12 years. No patients experienced status epilepticus. EEG patterns included a delayed maturation of EEG organization, irregular focal or diffuse slow activity, multifocal or diffuse epileptiform abnormalities. No structural epileptogenic lesions were detected at MRI. Valproate, lamotrigine, clobazam, topiramate and levetiracetam were the most used antiseizure medication. Complete seizure freedom was achieved only in 2 patients.

Conclusions: Onset of epilepsy after the first year of age, predominance of focal seizures with impaired awareness and generalized motor seizures, no pathognomonic underlying epileptic syndrome and infrequent occurrence of status epilepticus emerged as the main features of IQSEC2-related epilepsy phenotype.

Keywords: Children; Developmental and epileptic encephalopathies; Genetic epilepsies; Intellectual disability; Neurodevelopmental disorders.

Publication types

  • Multicenter Study

MeSH terms

  • Adolescent
  • Age of Onset
  • Anticonvulsants / therapeutic use
  • Child
  • Child, Preschool
  • Electroencephalography*
  • Epilepsy* / drug therapy
  • Epilepsy* / physiopathology
  • Female
  • Guanine Nucleotide Exchange Factors* / genetics
  • Humans
  • Infant
  • Italy
  • Male
  • Phenotype*
  • Retrospective Studies

Substances

  • Guanine Nucleotide Exchange Factors
  • IQSEC2 protein, human
  • Anticonvulsants