title: Neurodevelopmental outcome in Angelman syndrome: genotype-phenotype correlations.
abstract: Angelman syndrome (AS) is a neurogenetic disorder characterized by intellectual disability, developmental delay, lack of speech, and epileptic seizures. Previous studies have indicated that children with AS due to 15q11.2-q13 deletions have a more severe developmental delay and present more often autistic features than those with AS caused by other genetic etiologies. The present study investigated the neurodevelopmental profiles of the different genetic etiologies of AS, and examined the evolution of mental development and autistic features over a 12-year period in children with a 15q11.2-q13 deletion. This study included 42 children with AS. Twelve had a Class I deletion, 18 had Class II deletions, three showed atypical large deletions, five had paternal uniparental disomy (pUPD) and four had UBE3A mutations. Children with a deletion (Class I and Class II) showed significantly reduced developmental age in terms of visual perception, receptive language, and expressive language when compared to those with a UBE3A mutation and pUPD. Within all subgroups, expressive language performance was significantly reduced when compared to the receptive performance. A follow-up study of seven AS cases with 15q11.2-q13 deletions revealed that over 12 years, the level of autistic features did not change, but both receptive and expressive language skills improved.
authors.affiliation: Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark. Electronic address: linebiemertz@dadlnet.dk.
authors.forename: Line Granild Bie
authors.initials: LG
authors.lastname: Mertz
authors.affiliation: Psychiatric Hospital for Children and Adolescents, Aarhus University Hospital, Denmark.
authors.forename: Per
authors.initials: P
authors.lastname: Thaulov
authors.affiliation: Department of Psychology, Aarhus University, Denmark.
authors.forename: Anegen
authors.initials: A
authors.lastname: Trillingsgaard
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Denmark.
authors.forename: Rikke
authors.initials: R
authors.lastname: Christensen
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Denmark.
authors.forename: Ida
authors.initials: I
authors.lastname: Vogel
authors.affiliation: Department of Clinical Genetics, Odense University Hospital, Denmark.
authors.forename: Jens Michael
authors.initials: JM
authors.lastname: Hertz
authors.affiliation: Centre for Rare Diseases, Department of Pediatrics, Aarhus University Hospital, Denmark.
authors.forename: John R
authors.initials: JR
authors.lastname: Ostergaard
mesh_terms: D000367:Age Factors; D017204:Angelman Syndrome / Q000175:diagnosis* / Q000235:genetics*; D002648:Child; D002659:Child Development Disorders, Pervasive / Q000175:diagnosis / Q000235:genetics*; D002872:Chromosome Deletion; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D003718:Denmark; D002658:Developmental Disabilities / Q000175:diagnosis* / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics; D007805:Language Development Disorders / Q000175:diagnosis / Q000235:genetics; D008297:Male; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D010468:Perceptual Disorders / Q000175:diagnosis / Q000235:genetics; D011594:Psychometrics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D014796:Visual Perception / Q000235:genetics
chemical_list: C471639:UBE3A protein, human; D044767:Ubiquitin-Protein Ligases
keywords: 15q11.2-q13; ADOS; Angelman syndrome; Autism; Intellectual disability; Language skills; Mullen