Epilepsy and cataplexy in Angelman syndrome. Genotype-phenotype correlations

Res Dev Disabil. 2016 Sep:56:177-82. doi: 10.1016/j.ridd.2016.06.002.


Background: Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, epilepsy, and low threshold for laughter.

Aims: We investigated the occurrence and severity of epilepsy and laughter-induced loss of postural muscle tone determined by the different genetic subtypes.

Methods: This study included 39 children with AS. Deletion breakpoints were determined by high resolution CGH microarray (1×1M Agilent). Clinical data were based on a parent interview and medical record review.

Results: All patients with AS based on a deletion had epilepsy. Epilepsy was present in 3/4 children with UBE3A mutation, and 4/5 with pUPD. Onset of epilepsy occurred earlier in deletion cases compared to pUPD or UBE3A mutations cases. Laughter-induced postural muscle tone loss occurred only among deletion cases. We found no differences in severity of epilepsy between children with a larger Class I or a smaller Class II deletions, or between the total group with a deletion compared to children with pUPD or a UBE3A mutation. The drugs most frequently prescribed were benzodiazepines in monotherapy, or a combination of benzodiazepines and valproic acid.

Conclusion: Epilepsy is very common in patients with AS, especially in patients with a deletion. Postural muscle tone loss and collapsing during outbursts of laughter were seen in patients with a deletion only.

Keywords: 15q11.2–q13; Angelman syndrome; Cataplexy; Epilepsy; Seizures.

MeSH terms

  • Age of Onset
  • Angelman Syndrome / complications
  • Angelman Syndrome / genetics*
  • Base Sequence
  • Cataplexy / complications
  • Cataplexy / genetics*
  • Child
  • Chromosomes, Human, Pair 15 / genetics*
  • Comparative Genomic Hybridization
  • Denmark
  • Epilepsy / complications
  • Epilepsy / genetics*
  • Female
  • Genotype
  • Humans
  • Male
  • Mutation
  • Phenotype
  • Sequence Deletion
  • Ubiquitin-Protein Ligases / genetics*
  • Uniparental Disomy / genetics*


  • UBE3A protein, human
  • Ubiquitin-Protein Ligases