Abstracts

Rationale: Angelman Syndrome (AS) is a neurodevelopmental genetic disorder in which over 80% of those affected have epilepsy and abnormal EEGs, with typical abnormalities including rhythmic notched delta activity, rhythmic 4-6 Hz theta activity, and diffuse 2-3 Hz spike and slow wave activity. Phenotypic variation exists amongst genetic subtypes of AS in terms of epilepsy and neurocognitive functioning, but few studies have examined EEG findings by genetic subtype. The purpose of this study was to assess EEG findings in AS by genetic subtype and to assess the relationship between the severity of an individual’s EEG findings and their clinical epilepsy. Methods: EEGs and clinical histories of children with AS were collected from the AS Clinic at Massachusetts General Hospital as well as from a larger study done at MGH through the Angelman Syndrome Foundation (ASF) assessing the natural history and treatment of epilepsy in this population. EEGs were scored using the scoring system created by the AS Rare Disease Clinical Research Consortium, and clinical epilepsies were scored using the Early Childhood Epilepsy Severity Scale (E-Chess). The Spearman’s Rank Order Correlation (non-parametric) was used to analyze the correlation between the two scores. Results: EEGs were collected from 14 patients with AS (5 with maternal deletions, 4 with clinical diagnoses, 3 with UBE3A mutations, and 2 with UPD). Individuals with maternal deletions (7.6) and clinical diagnoses (7.5) had the highest E-Chess scores followed by those with UPD (6) and UBE3A (0.67). Those with UPD (8) and maternal deletions (7.8) had the highest EEG severity scores followed by those with clinical diagnoses (5) and UBE3A (4.67). All EEGs were at least mildly abnormal with background slowing present in 12/14 EEGs (1 deletion and 1 clinical diagnosis had normal backgrounds). Epileptiform discharges were present in 4/5 with deletions, 2/4 with clinical diagnoses, 0/3 with UBE3A and 2/2 with UPD. Notched 2-3 Hz delta activity was present in 4/5 with deletions, 1/4 with clinical diagnoses, 2/3 with UBE3A, and 1/2 with UPD. The correlation between EEG severity and epilepsy severity was not statistically significant (p=0.416). Conclusions: Clinical epilepsy was most severe in those with deletions and clinical diagnoses, consistent with previous reports. Typical EEG findings of AS were most commonly seen in those with maternal deletions, which has been previously reported, and also in UPD, which has not been previously reported, but the sample size for this subtype was very small (n=2). While EEG severity was not significantly associated with epilepsy severity, those with more severe EEG findings tended to have more severe clinical epilepsy. The correlation would have been stronger (p=0.168), though still not statistically significant, with the removal of two statistical outliers with high EEG severity and no clinical epilepsy. Analysis in a large population is needed to better assess this relationship. It is also unknown whether EEG severity is associated with neuropsychological functioning, behavior, or sleep disturbances. Again, further studies of larger populations are needed.