CORTICAL MYOCLONUS IN ANGELMAN SYNDROME

Angelman syndrome (AS) results from lack of genetic contribution from maternal chromosome 15q11-13. This region encompasses three GABA(A) re ceptor subunit genes (beta 3, (alpha 5, and gamma 3). The characterist ic phenotype of AS is severe mental retardation, ataxic gait, tremulou sness, and jerky movements. We studied the movement disorder in 11 AS patients, aged 3 to 28 years. Two patients had paternal uniparental di somy for chromosome 15, 8 had a >3 Mb deletion, and 1 had a microdelet ion involving loci D15S10, D15S113, and GABRB3. All patients exhibited quasicontinuous rhythmic myoclonus mainly involving hands and face, a ccompanied by rhythmic 5- to 10-Hz electroencephalographic (EEG) activ ity. Electromyographic bursts lasted 35 +/- 13 msec and had a frequenc y of 11 +/- 2.4 Hz. Burst-locked EEG averaging in 5 patients, generate d a premyoclonus transient preceding the burst by 19 +/- 5 msec. A cor tical spread pattern of myoclonic cortical activity was observed. Seve n patients also demonstrated myoclonic seizures. No giant somatosensor y evoked potentials or C-reflex were observed. The silent period follo wing motor evoked potentials was shortened by 70%, indicating motor co rtex hyperexcitability. Treatment with piracetam in 5 patients signifi cantly improved myoclonus. We conclude that spontaneous, rhythmic, fas t-bursting cortical myoclonus is a prominent feature of AS.