Two mutations in the nicotinic acetylcholine receptor subunit A4 (CHRNA4) in a family with autosomal dominant sleep-related hypermotor epilepsy

Epileptic Disord. 2020 Feb 1;22(1):116-119. doi: 10.1684/epd.2020.1140.


Sleep-related hypermotor epilepsy, or nocturnal frontal lobe epilepsy, as it was formerly called, is a focal epilepsy with mostly sleep-related seizures of hypermotor, tonic or dystonic semiology. Sleep-related hypermotor epilepsy may be attributed to a monogenetic cause with autosomal dominant inheritance. Mutations are described in different genes, including the genes for three subunits of the nicotinic acetylcholine receptor. We present a family with members over four generations exhibiting sleep-related hypermotor epilepsy. Genetic testing was available for three members from three generations, and revealed two variants in the alpha-4 subunit of the nicotinic acetylcholine receptor (one of them being novel) which are likely to be disease-causing. As these mutations were identified in cis configuration (on the same allele), we do not know whether one of the variants alone or a combination of the two is responsible for the pathogenicity.

Keywords: ADNFLE; CHRNA4; hypermotor seizure; nicotinic acetylcholine receptor; nocturnal seizure.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Aged
  • Epilepsies, Partial* / complications
  • Epilepsies, Partial* / genetics
  • Epilepsies, Partial* / physiopathology
  • Female
  • Humans
  • Middle Aged
  • Pedigree
  • Receptors, Nicotinic / genetics*
  • Sleep Arousal Disorders* / etiology
  • Sleep Arousal Disorders* / genetics
  • Sleep Arousal Disorders* / physiopathology
  • Young Adult


  • Receptors, Nicotinic
  • nicotinic acetylcholine receptor alpha4 subunit