The natural history and response to treatment of epilepsy in a large population of Angelman syndrome (AS) patients were studied by detailed electronic survey conducted through the AS Foundation by pediatric neurologists at Massachusetts General Hospital, Boston; Texas Southwestern Medical Center; and Rady Children’s Hospital, San Diego, CA. Approximately 1000 families of individuals with AS were asked to complete a questionnaire online. The survey was available for 3 months, Feb–May 2007, and questions included the description of seizures, and response to various medications and their side effects. Responses were obtained from family members of 461 individuals with AS, a 40-50% response rate. The average age of patients was 11.8 years (1.3-45 years) at time of survey, and an average age of 5.3 years (<1-35 years) at diagnosis; 56% were male. Multiple seizure types were reported, most commonly atonic seizures (41%), generalized tonic-clonic (40%), atypical absence seizures (37%), and complex partial (32%). Myoclonic seizures occurred in 12% and infantile spasms in 2%. Control of seizures was reported in 34% for a median period of 3.2 years, usually beginning at 8.8 years of age. Of 396 with current epilepsy, only 46% of those age <3 years had seizures, whereas 53-64% ages 3-18 years had seizures; 35% had regression in development, and 12% had experienced convulsive status epilepticus. In 64% of subjects with epilepsy, emergency lorazepam or diazepam was used for prolonged seizures or clusters of seizures.

Rates of epilepsy differed among genetic subtypes; those with maternal deletions (89%) and unknown subtypes (90%) had the highest rates of epilepsy, whereas those with imprinting defects (55%) were least affected. Of all subjects, 65% had a maternal deletion, and 18% had an unknown subtype. Most commonly prescribed anticonvulsant medications (AED) were valproic acid (63%) and clonazepam (34%), but lamotrigine (24%) and levetiracetam (20%) had similar efficacy and tolerability. Only 15% responded to the initial AED, and an additional 8% responded to the second agent; 77% had refractory seizures. Ketogenic diet was effective in 11 of 31 subjects, and vagus nerve stimulation in 8 of 16. [1]

COMMENT. Epilepsy is a common problem in AS and is refractory to treatment. Although often considered a generalized form of epilepsy, partial seizures are fairly frequent. Newer AEDs, lamotrigine and levetiracetam, are as effective as conventional medications and have fewer serious side effects. Genetic analyses are correlated with response to therapy.

Sleep problems associated with epilepsy in AS may be related to the severity of seizures and the use of anticonvulsant mdication. In 290 individuals with AS, decreased nightly hours of sleep, and a difficulty initiating sleep were significantly correlated with epilepsy. [2]

Genetic testing in AS demonstrates a molecular mechanism causing lack of expression of the UBE3A gene with abnormalities of chromosome 15, inherited from the mother [3]. Three characteristic EEG patterns are described: A. high amplitude delta with spikes anteriorly without clinical correlation; B. diffuse theta not associated with drowsiness; and C. high amplitude delta mixed with spikes in posterior regions on eye closure. Boyd SG and associates described the EEG features in early diagnosis of AS. [4]