Gea Beunders1, Jiddeke van de Kamp1, Pradeep Vasudevan2, Jenny Morton3, Katrien Smets4, Tjitske Kleefstra5, Sonja A de Munnik5, Janneke Schuurs-Hoeijmakers5, Berten Ceulemans6, Marcella Zollino7, Sabine Hoffjan8, Stefan Wieczorek8, Joyce So9, Leanne Mercer10, Tanya Walker10, Lea Velsher11, Michael J Parker12, Alex C Magee13, Bart Elffers14, R Frank Kooy15, Helger G Yntema5, Elizabeth J Meijers-Heijboer1, Erik A Sistermans1. 1. Department of Clinical Genetics, VU University Medical Center Amsterdam, The Netherlands. 2. Department of Clinical Genetics, University Hospitals of Leicester, Leicester, UK. 3. Department of Clinical Genetics, Birmingham Women's Hospital, Edgbaston, Birmingham, UK. 4. 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. 5. Department of Human Genetics, Radboud University Medical Centre, Nijmegen, The Netherlands. 6. Department of Neurology- Paediatric Neurology, University and University Hospital Antwerp, Antwerp, Belgium. 7. Institute of Medical Genetics, 'A. Gemelli' School of Medicine, Catholic University Rome, Italy. 8. Department of Human Genetics, Ruhr-University Bochum, Bochum, Germany. 9. 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. 10. Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada. 11. Northwestern Ontario Regional Genetics Program, Thunder Bay District Health Unit, Thunder Bay, Canada Genetics Program, North York General Hospital, Toronto, Canada. 12. Department of Clinical Genetics, Sheffield Children's Hospital, Sheffield, UK. 13. Genetic Medicine, Belfast City Hospital, Belfast, UK. 14. Department of Medical Care for Patients with Intellectual Disability, AMSTA, Amsterdam, The Netherlands. 15. Department of Medical Genetics, University and University Hospital Antwerp, Antwerp, Belgium.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/
Authors: Sanxiong Liu; Kimberly A Aldinger; Chi Vicky Cheng; Takae Kiyama; Mitali Dave; Hanna K McNamara; Wukui Zhao; James M Stafford; Nicolas Descostes; Pedro Lee; Stefano G Caraffi; Ivan Ivanovski; Edoardo Errichiello; Christiane Zweier; Orsetta Zuffardi; Michael Schneider; Antigone S Papavasiliou; M Scott Perry; Jennifer Humberson; Megan T Cho; Astrid Weber; Andrew Swale; Tudor C Badea; Chai-An Mao; Livia Garavelli; William B Dobyns; Danny Reinberg Journal: Mol Cell Date: 2021-10-11 Impact factor: 17.970
Authors: Laura Machado Lara Carvalho; Carla Sustek D'Angelo; Darine Villela; Silvia Souza da Costa; Alexander Augusto de Lima Jorge; Israel Tojal da Silva; Marília de Oliveira Scliar; Luiza Dias Chaves; Ana Cristina Victorino Krepischi; Celia Priszkulnik Koiffmann; Carla Rosenberg Journal: Int J Obes (Lond) Date: 2022-05-21 Impact factor: 5.551
Authors: Pritmohinder S Gill; Harsh Dweep; Shannon Rose; Priyankara J Wickramasinghe; Kanan K Vyas; Sandra McCullough; Patricia A Porter-Gill; Richard E Frye Journal: J Pers Med Date: 2022-06-01
Authors: Michael Lugo; Zoë C Wong; Charles J Billington; Phoebe C R Parrish; Glennis Muldoon; Delong Liu; Barbara R Pober; Beth A Kozel Journal: Am J Med Genet A Date: 2020-02-20 Impact factor: 2.578
Authors: Ilse Meerschaut; Sarah Vergult; Annelies Dheedene; Björn Menten; Katya De Groote; Hans De Wilde; Laura Muiño Mosquera; Joseph Panzer; Kristof Vandekerckhove; Paul J Coucke; Daniël De Wolf; Bert Callewaert Journal: Genes (Basel) Date: 2021-07-08 Impact factor: 4.096