Epilepsy and cataplexy in Angelman syndrome. Genotype-phenotype correlations.
BACKGROUND
Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, epilepsy, and low threshold for laughter.


OBJECTIVE
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.


CONCLUSIONS
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.
Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark. Electronic address: linebiemertz@dadlnet.dk.
Line
L
Granild Bie Mertz
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Rikke
R
Christensen
Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
Ida
I
Vogel
Department of Clinical Genetics, Odense University Hospital, Odense, Denmark.
Jens Michael
JM
Hertz
Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark.
John R
JR
Østergaard
D017668:Age of Onset; D017204:Angelman Syndrome / Q000150:complications / Q000235:genetics*; D001483:Base Sequence; D002385:Cataplexy / Q000150:complications / Q000235:genetics*; D002648:Child; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D055028:Comparative Genomic Hybridization; D003718:Denmark; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009154:Mutation; D010641:Phenotype; D017384:Sequence Deletion; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics*
C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
15q11.2–q13; Angelman syndrome; Cataplexy; Epilepsy; Seizures