title: Angelman syndrome: Mutations influence features in early childhood.
abstract: Angelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternal copy of UBE3A. Although the "classic" features of AS are well described, few large-scale studies have delineated the clinical features in AS. We present baseline data from 92 children with a molecular diagnosis of AS between 5 and 60 months old who are enrolled in the National Institutes of Health Rare Diseases Clinical Research Network Angelman Syndrome Natural History Study from January 2006 to March 2008. Seventy-four percent of participants had deletions, 14% had either uniparental disomy (UPD) or imprinting defects, and 12% had UBE3A mutations. Participants with UPD/imprinting defects were heavier (P = 0.0002), while those with deletions were lighter, than the general population (P < 0.0001). Twenty out of 92 participants were underweight, all of whom had deletions or UBE3A mutations. Eight out of 92 participants (6/13 (46%) with UPD/imprinting defects and 2/11 (18%) with UBE3A mutations) were obese. Seventy-four out of 92 participants (80%) had absolute or relative microcephaly. No participant was macrocephalic. The most common behavioral findings were mouthing behavior (95%), short attention span (92%), ataxic or broad-based gait (88%), history of sleep difficulties (80%), and fascination with water (75%). Frequent, easily provoked laughter was observed in 60%. Clinical seizures were reported in 65% of participants but all electroencephalograms (EEGs) were abnormal. We conclude that the most characteristic feature of AS is the neurobehavioral phenotype, but specific EEG findings are highly sensitive for AS. Obesity is common among those with UPD/imprinting defects.
authors.affiliation: Children's Hospital Boston, Harvard Medical School, Massachusetts, USA.
authors.forename: Wen-Hann
authors.initials: WH
authors.lastname: Tan
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Steven A
authors.initials: SA
authors.lastname: Skinner
authors.forename: Irina
authors.initials: I
authors.lastname: Anselm
authors.forename: Rene
authors.initials: R
authors.lastname: Barbieri-Welge
authors.forename: Astrid
authors.initials: A
authors.lastname: Bauer-Carlin
authors.forename: Arthur L
authors.initials: AL
authors.lastname: Beaudet
authors.forename: Terry Jo
authors.initials: TJ
authors.lastname: Bichell
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Gentile
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Glaze
authors.forename: Lucia T
authors.initials: LT
authors.lastname: Horowitz
authors.forename: Sanjeev V
authors.initials: SV
authors.lastname: Kothare
authors.forename: Hye-Seung
authors.initials: HS
authors.lastname: Lee
authors.forename: Mark P
authors.initials: MP
authors.lastname: Nespeca
authors.forename: Sarika U
authors.initials: SU
authors.lastname: Peters
authors.forename: Trilochan
authors.initials: T
authors.lastname: Sahoo
authors.forename: Dean
authors.initials: D
authors.lastname: Sarco
authors.forename: Susan E
authors.initials: SE
authors.lastname: Waisbren
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Bird
mesh_terms: D017204:Angelman Syndrome / Q000235:genetics* / Q000473:pathology*; D002675:Child, Preschool; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003625:Data Collection; D004569:Electroencephalography; D006801:Humans; D007223:Infant; D008137:Longitudinal Studies; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D018709:Statistics, Nonparametric; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases