Cortical myoclonus in Angelman syndrome

Angelman syndrome (AS) results from lack of genetic contribution from maternal chromosome 15q11-13. This region encompasses three GABAA receptor subunit genes (beta3, alpha5, and gamma3). The characteristic phenotype of AS is severe mental retardation, ataxic gait, tremulousness, and jerky movements. We studied the movement disorder in 11 AS patients, aged 3 to 28 years. Two patients had paternal uniparental disomy for chromosome 15, 8 had a >3 Mb deletion, and 1 had a microdeletion involving loci D15S10, D15S113, and GABRB3. All patients exhibited quasicontinuous rhythmic myoclonus mainly involving hands and face, accompanied by rhythmic 5- to 10-Hz electroencephalographic (EEG) activity. Electromyographic bursts lasted 35 +/- 13 msec and had a frequency of 11 +/- 2.4 Hz. Burst-locked EEG averaging in 5 patients, generated a premyoclonus transient preceding the burst by 19 +/- 5 msec. A cortical spread pattern of myoclonic cortical activity was observed. Seven patients also demonstrated myoclonic seizures. No giant somatosensory evoked potentials or C-reflex were observed. The silent period following motor evoked potentials was shortened by 70%, indicating motor cortex hyperexcitability. Treatment with piracetam in 5 patients significantly improved myoclonus. We conclude that spontaneous, rhythmic, fast-bursting cortical myoclonus is a prominent feature of AS.