title: A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype.
abstract: AUTS2 syndrome is an 'intellectual disability (ID) syndrome' caused by genomic rearrangements, deletions, intragenic duplications or mutations disrupting AUTS2. So far, 50 patients with AUTS2 syndrome have been described, but clinical data are limited and almost all cases involved young children.
  
  
  
  We present a detailed clinical description of 13 patients (including six adults) with AUTS2 syndrome who have a pathogenic mutation or deletion in AUTS2. All patients were systematically evaluated by the same clinical geneticist.
  
  
  
  All patients have borderline to severe ID/developmental delay, 83-100% have microcephaly and feeding difficulties. Congenital malformations are rare, but mild heart defects, contractures and genital malformations do occur. There are no major health issues in the adults; the oldest of whom is now 59 years of age. Behaviour is marked by it is a friendly outgoing social interaction. Specific features of autism (like obsessive behaviour) are seen frequently (83%), but classical autism was not diagnosed in any. A mild clinical phenotype is associated with a small in-frame 5' deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the full-length AUTS2 transcript give a more severe phenotype and occur de novo.
  
  
  
  The 13 patients with AUTS2 syndrome with unique pathogenic deletions scattered around the AUTS2 locus confirm a phenotype-genotype correlation. Despite individual variations, AUTS2 syndrome emerges as a specific ID syndrome with microcephaly, feeding difficulties, dysmorphic features and a specific behavioural phenotype.
authors.affiliation: Department of Clinical Genetics, VU University Medical Center Amsterdam, The Netherlands.
authors.forename: Gea
authors.initials: G
authors.lastname: Beunders
authors.affiliation: Department of Clinical Genetics, VU University Medical Center Amsterdam, The Netherlands.
authors.forename: Jiddeke
authors.initials: J
authors.lastname: van de Kamp
authors.affiliation: Department of Clinical Genetics, University Hospitals of Leicester, Leicester, UK.
authors.forename: Pradeep
authors.initials: P
authors.lastname: Vasudevan
authors.affiliation: Department of Clinical Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham, UK.
authors.forename: Jenny
authors.initials: J
authors.lastname: Morton
authors.affiliation: Department of Neurology, Antwerp University Hospital, Antwerp, Belgium Neurogenetics Group, VIB-Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium Laboratories of Neurogenetics and Neuropathology, Institute Born-Bunge, University of Antwerp, Antwerp, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Smets
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Tjitske
authors.initials: T
authors.lastname: Kleefstra
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Sonja A
authors.initials: SA
authors.lastname: de Munnik
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Janneke
authors.initials: J
authors.lastname: Schuurs-Hoeijmakers
authors.affiliation: Department of Neurology- Paediatric Neurology, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.affiliation: Institute of Medical Genetics, 'A. Gemelli' School of Medicine, Catholic University Rome, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: Zollino
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Sabine
authors.initials: S
authors.lastname: Hoffjan
authors.affiliation: Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieczorek
authors.affiliation: Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada The Fred A. Litwin Family Centre in Genetic Medicine, University Health Network and Mount Sinai Hospital, Toronto, Canada Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada.
authors.forename: Joyce
authors.initials: J
authors.lastname: So
authors.affiliation: Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada.
authors.forename: Leanne
authors.initials: L
authors.lastname: Mercer
authors.affiliation: Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada.
authors.forename: Tanya
authors.initials: T
authors.lastname: Walker
authors.affiliation: Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada Genetics Program, North York General Hospital, Toronto, Canada.
authors.forename: Lea
authors.initials: L
authors.lastname: Velsher
authors.affiliation: Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield, UK.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Parker
authors.affiliation: Genetic Medicine, Belfast City Hospital, Belfast, UK.
authors.forename: Alex C
authors.initials: AC
authors.lastname: Magee
authors.affiliation: Department of Medical Care for Patients with Intellectual Disability, AMSTA, Amsterdam, The Netherlands.
authors.forename: Bart
authors.initials: B
authors.lastname: Elffers
authors.affiliation: Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
authors.forename: R Frank
authors.identifier: 0000-0003-2024-0485
authors.initials: RF
authors.lastname: Kooy
authors.affiliation: Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: Helger G
authors.initials: HG
authors.lastname: Yntema
authors.affiliation: Department of Clinical Genetics, VU University Medical Center Amsterdam, The Netherlands.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Meijers-Heijboer
authors.affiliation: Department of Clinical Genetics, VU University Medical Center Amsterdam, The Netherlands.
authors.forename: Erik A
authors.initials: EA
authors.lastname: Sistermans
mesh_terms: D000328:Adult; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D005091:Exons / Q000235:genetics; D005260:Female; D056726:Genetic Association Studies / Q000379:methods; D057895:Haploinsufficiency / Q000235:genetics; D006801:Humans; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D001523:Mental Disorders / Q000235:genetics*; D008831:Microcephaly / Q000235:genetics; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011506:Proteins / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D013577:Syndrome; D014157:Transcription Factors; D055815:Young Adult
chemical_list: C554283:AUTS2 protein, human; D003598:Cytoskeletal Proteins; D011506:Proteins; D014157:Transcription Factors
keywords: Clinical genetics; Copy-number; Developmental; Genetics; Psychiatry