Cryptogenic epileptic syndromes related to SCN1A: twelve novel mutations identified

Arch Neurol. 2008 Apr;65(4):489-94. doi: 10.1001/archneur.65.4.489.


Background: Sodium channel alpha 1 subunit gene, SCN1A, is the gene encoding the neuronal voltage-gated sodium channel alpha 1 subunit (Na(v)1.1) and is mutated in different forms of epilepsy. Mutations in this gene were observed in more than 70% of patients with severe myoclonic epilepsy of infancy (SMEI) and were also found in different types of infantile epileptic encephalopathy.

Objective: To search for disease-causing mutations in SCN1A in patients with cryptogenic epileptic syndromes (ie, syndromes with an unknown cause).

Design: Clinical characterization and molecular genetic analysis of a cohort of patients.

Setting: University hospitals, rehabilitation centers, and molecular biology laboratories.

Patients: Sixty unrelated patients with cryptogenic epileptic syndromes.

Main outcome measures: Samples of DNA were analyzed for mutations and for large heterozygous deletions encompassing the SCN1A gene. A search for microdeletions in the SCN1A gene was also performed in the subset of patients with SMEI/SMEI-borderland who had negative results at the point mutation screening.

Results: No large deletions at the SCN1A locus were found in any of the patients analyzed. In contrast, 13 different point mutations were identified in 12 patients: 10 with SMEI, 1 with generalized epilepsy with febrile seizures plus, and 1 with cryptogenic focal epilepsy. An additional search for SCN1A intragenic microdeletions in the remaining patients with SMEI/SMEI-borderland and no point mutations was also negative.

Conclusions: These results confirm the role of the SCN1A gene in different types of epilepsy, including cryptogenic epileptic syndromes. However, large deletions encompassing SCN1A were not common disease-causing rearrangements in this group of epilepsies.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Child
  • Child, Preschool
  • Chromosome Deletion
  • DNA Mutational Analysis*
  • Epilepsies, Myoclonic / diagnosis
  • Epilepsies, Myoclonic / genetics
  • Epilepsies, Partial / diagnosis
  • Epilepsies, Partial / genetics
  • Epilepsy / diagnosis
  • Epilepsy / genetics*
  • Epilepsy, Generalized / diagnosis
  • Epilepsy, Generalized / genetics
  • Female
  • Follow-Up Studies
  • Genetic Carrier Screening
  • Genotype
  • Humans
  • Infant
  • Male
  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins / genetics*
  • Phenotype
  • Point Mutation
  • Seizures, Febrile / diagnosis
  • Seizures, Febrile / genetics
  • Sodium Channels / genetics*


  • NAV1.1 Voltage-Gated Sodium Channel
  • Nerve Tissue Proteins
  • SCN1A protein, human
  • Sodium Channels