Epilepsy in patients with angelman syndrome caused by deletion of the chromosome 15q11-13.
BACKGROUND
Angelman syndrome (AS) is a neurogenetic disorder characterized by severe mental retardation, speech disorder, stereotyped jerky movements, and a peculiar behavioral profile, with a happy disposition and outbursts of laughter. Most patients with AS present with epilepsy and suggestive electroencephalographic patterns, which may be used as diagnostic criteria.


OBJECTIVE
To study epilepsy and response to treatment in a series of patients with AS determined by deletion.


METHODS
Parent and caregiver interview and medical record review.


METHODS
Epilepsy Center at the University of São Paulo.


METHODS
Nineteen patients with AS determined by deletion of chromosome 15q11-13.


METHODS
Epilepsy severity, epilepsy evolution, and response to antiepileptic drug treatment.


RESULTS
All patients with AS in this group had generalized epilepsy, and 10 (53%) also had partial epilepsy. Main seizure types were atypical absences and myoclonic and tonic-clonic seizures. Mean age at onset was 1 year 1 month. Epilepsy aggravated by fever occurred in 10 patients (53%) and status epilepticus in 16 (84%). Eighteen patients (95%) had previous or current history of daily seizures, of which 14 (64%) had disabling seizures. Multiple seizure types were observed in 13 patients (53%). History of refractory epilepsy was reported in 16 patients (84%). Parents reported improvement, characterized by decrease in seizure frequency or seizure control, at the mean age of 5.3 years. Therefore, most of these patients had a period of refractory epilepsy; however, improvement occurred during late childhood and puberty. The best therapeutic response was obtained with valproic acid alone or in association with phenobarbital or clonazepam. Epilepsy was aggravated by carbamazepine, oxcarbazepine, and vigabatrin.


CONCLUSIONS
Patients with AS with deletion have epilepsy with early onset and stereotyped electroclinical profile regarding seizure type, severity, and response to antiepileptic drug treatment. Another feature of AS is the age-related improvement, even in refractory cases, during late childhood and puberty. These characteristics are not specific to this syndrome but, when inserted in the proper clinical context, may anticipate diagnosis. We believe that AS should be considered a differential diagnosis in developmentally delayed infants with severe, generalized, cryptogenic epilepsy; however, a proper electroclinical delineation of each genetic group is mandatory.
Valente
Kette D
KD
Laboratory of Clinical Neurophysiology, Institute and Department of Psychiatry, University of São Paulo, São Paulo, Brazil. kettevalente@msn.com
Koiffmann
Célia P
CP
Fridman
Cíntia
C
Varella
Mônica
M
Kok
Fernando
F
Andrade
Joaquina Queiroz
JQ
Grossmann
Rosi M
RM
Marques-Dias
Maria Joaquina
MJ
D000293:Adolescent; D017668:Age of Onset; D017204:Angelman Syndrome / Q000150:complications*; D000927:Anticonvulsants / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D004252:DNA Mutational Analysis / Q000379:methods; D018450:Disease Progression; D004569:Electroencephalography / Q000379:methods; D004827:Epilepsy / Q000145:classification / Q000188:drug therapy / Q000209:etiology* / Q000235:genetics*; D005260:Female; D005334:Fever / Q000209:etiology; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D016896:Treatment Outcome
D000927:Anticonvulsants