Electroclinical characteristics of seizures-comparing Prader--Willi syndrome with Angelman syndrome

Abstract

Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are two clinically distinct neurobehavioral syndromes that are caused by deficiency of gene expression from paternally or maternally derived homologues on chromosome 15q11-q13, respectively. Clinical and genetic heterogeneities are common in both syndromes and they are now regarded as 'sister genetic imprinting syndromes'. This study aimed to describe and compare the electroclinical characteristics of seizures between PWS and AS, and to try to explore the possible mechanisms of epileptogenesis in these two syndromes. Fifty patients with genetically documented PWS and 18 patients with a putative diagnosis of AS were included in this study. These patients were diagnosed on the basis of characteristic physical findings and their neurobehavioral phenotype, as well as cytogenetic and molecular studies. Epileptic seizures were present in 16 of 18 patients with AS, but in only eight of 50 patients with PWS. Using electroencephalography (EEG), the most characteristic findings for AS were rhythmic 2-3 Hz delta waves of high-amplitude that were maximal over the frontal regions, and 3-4 Hz spikes and sharp wave runs posteriorly. These were never seen in PWS. Patients with AS had a much higher incidence of seizures with characteristic EEG findings, similar to those seen in mice that are deficient in a single gene (UBE3A) that displays regional brain-specific imprinting in humans and mice. In this series, cases with no detectable cytogenetic or molecular defect at the AS locus displayed similar AS phenotype, seizure severity and EEG abnormalities compared to those with such a defect. Thus, the UBE3A gene is presumed to be potentially involved in the epileptogenesis of AS. It is also possible that UBE3A and another gene located nearby, gamma-aminobutyric receptorbeta3 subunit, may interact in some way, and result in the severe epilepsy seen with AS. Some patients with PWS and AS share the common EEG features of persistent high-amplitude 4-6 Hz activity in recordings during sleep, and while awake. The significance of such EEG findings needs further experience to clarity.