Angelman syndrome caused by deletion: a genotype-phenotype correlation determined by breakpoint.
OBJECTIVE
Deletion of the chromosome 15q11-q13, the most common genetic mechanism associated with Angelman syndrome (AS), is highly associated with a severe phenotype. However, deletion is not a genetically homogeneous group as it is composed by two main groups: Class I with breakpoints at BP1 (proximal) and BP3 (distal) and Class II present breakpoints at BP2 (proximal) and BP3 (distal). In this study, we aimed to evaluate the impact of the breakpoint on the electroclinical profile.


METHODS
We evaluated 16 patients with AS caused by 15q11-13 deletion (6 were Class I; 10 were Class II). We characterized epilepsy features by clinical history obtained from parents and caretakers with a pre-standard questionnaire. These data were corroborated by medical records, contact with previous physicians, and video-EEG monitoring. Suggestive EEG patterns for AS were classified according to the classical description of Boyd et al. (1988).


RESULTS
AS patients with BP1-BP3 deletion had significantly more daily and disabling seizures than AS patients with BP1-BP2 deletion. They also presented a significant higher frequency of status epilepticus and epilepsy aggravated by fever. Need for polytherapy was significantly more frequent in BP1-BP3 patients. EEG features were similar in both groups.


CONCLUSIONS
This study shows a significant correlation between the two deletion classes and AS clinical, but not the electrographic phenotype. Epilepsy is more severe and refractory to treatment in patients with larger deletions. Deletion is not a homogeneous group and knowledge on the breakpoint may have a clinical implication and represent an important factor in parental counseling.
Laboratory of Clinical Neurophysiology, Institute and Department of Psychiatry, University of São Paulo, São Paulo, SP, Brazil. kettevalente@msn.com
Kette D
KD
Valente
Monica Castro
MC
Varela
Celia Priszkulnik
CP
Koiffmann
Joaquina Queiroz
JQ
Andrade
Rosi
R
Grossmann
Fernando
F
Kok
Maria Joaquina
MJ
Marques-Dias
D017204:Angelman Syndrome / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D056905:Chromosome Breakpoints; D004569:Electroencephalography / Q000379:methods; D005500:Follow-Up Studies; D017353:Gene Deletion; D056726:Genetic Association Studies / Q000379:methods*; D006801:Humans; D011446:Prospective Studies