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, γ-aminobutyric receptorβ3 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.
Keywords
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Article info
Publication history
Accepted:
November 5,
2003
Received in revised form:
October 28,
2003
Received:
July 14,
2003
Footnotes
☆The paper is based on the lecture given at the 6th annual meeting of the Infantile Seizure Society, Tokyo, March 15–16, 2003.
Identification
Copyright
© 2004 Elsevier B.V. Published by Elsevier Inc. All rights reserved.
