Abstract
Angelman syndrome (AS) has emerged as an important neurogenetic syndrome due to its
relatively high prevalence and easier confirmation of the diagnosis by improved genetic
testing. In infancy, nonspecific clinical features of AS pose diagnostic challenges
to the neurologist and these include any combination of microcephaly, seizure disorder,
global developmental delay or an ataxic/hypotonic cerebral palsy-like picture. In
later childhood, however, absent speech, excessively happy behavior, ataxia and jerky
movements usually present as a recognizable clinical syndrome. Brain MRI shows nonspecific
or normal findings but occasionally the characteristic EEG patterns alone can lead
to the correct diagnosis. The physical, clinical and behavioral aspects appear to
be attributable to localized CNS dysfunction of the ubiquitin ligase gene, UBE3A, located at 15q11.2. In certain brain regions, UBE3A normally has mono-allelic expression
from the maternally derived chromosome 15. Several distinct genetic mechanisms can
inactivate or disrupt the maternally derived UBE3A: chromosome microdeletions, paternal
uniparental disomy, imprinting defects and intragenic UBE3A mutations. Those with
the deletion type of AS are the most prevalent (about 70% of cases) and appear to
have a more severe clinical phenotype. The unique epileptic patterns and distinct
behavioral features may be related to multiple actions of UBE3A, possibly occurring
during, as well as after, the time of neuronal development.
Keywords
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Article info
Publication history
Accepted:
September 23,
2003
Received in revised form:
September 22,
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.
