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. DESIGN: Parent and caregiver interview and medical record review. SETTING: Epilepsy Center at the University of São Paulo. PATIENTS: Nineteen patients with AS determined by deletion of chromosome 15q11-13. MAIN OUTCOME MEASURES: 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.

Angelman syndrome: uniparental paternal disomy 15 determines mild epilepsy, but has no influence on EEG patterns.

The authors describe the electroclinical phenotype of four patients with Angelman syndrome (AS) determined by its rarest genetic mechanism-uniparental disomy (UPD). The analysis of ours and published patients showed that in UPD, when epilepsy occurred, it was milder compared to patients with deletion, although a suggestive EEG was observed in most patients. We found that UPD patients do not completely fit the scenario delineated for AS, suggesting that patients determined by different mechanisms should be distinctly addressed, for a better understanding of this syndrome.

Angelman syndrome: difficulties in EEG pattern recognition and possible misinterpretations.

PURPOSE: This study aimed to evaluate the sensitivity of the EEG in Angelman syndrome (AS), to verify the age at onset of suggestive EEGs and to study EEG patterns, analyzing variations and comparing our findings with nomenclature previously used. METHODS: Seventy EEG and 15 V-EEGs of 26 patients were analyzed. Suggestive EEG patterns of AS were classified in delta pattern (DP), theta pattern (TP), and posterior discharges (PDs). Generic terms were used to simplify the analysis. RESULTS: Suggestive EEGs were observed in 25 (96.2%) patients. DP occurred in 22 patients with four variants-hypsarrhythmic-like: irregular, high-amplitude, generalized delta activity (DA) with multifocal epileptiform discharges (EDs); slow variant: regular, high-amplitude, generalized DA with rare EDs; ill-defined slow spike-and-wave: regular, high-amplitude, generalized DA with superimposed EDs characterizing a slow wave, with notched appearance; triphasic-like: rhythmic, moderate-amplitude DA over anterior regions with superimposed EDs. TP was observed in eight patients, as generalized or over the posterior regions. PDs were seen in 19 patients as runs of sharp waves or runs of high-amplitude slow waves with superimposed EDs. TP was the only age-related pattern (younger than 8 years) and observed only in patients with deletion. In 15 patients who had an EEG before the clinical diagnosis, 60% had a suggestive tracing. CONCLUSIONS: Although some EEG descriptions are not very detailed, and every author describes findings in a slightly different manner, obviously a common denominator must exist. In this context, EEG seems to be a very sensitive method for the diagnosis of AS, offering an opportunity to corroborate this etiologic diagnosis. Conversely, we do not believe that these patterns may be accounted as specific, except for the delta pattern, which seems to be extremely unusual in other syndromes. Other EEG patterns observed in AS, such as theta activity and PDs, occur in a wide variety of disorders. Nonetheless, their importance for the EEG diagnosis of AS is supported by the fact that they are associated with other features and may be helpful in a proper clinical setting.