RT Journal Article
SR Electronic
T1 A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype
JF Journal of Medical Genetics
JO J Med Genet
FD BMJ Publishing Group Ltd
SP 523
OP 532
DO 10.1136/jmedgenet-2015-103601
VO 53
IS 8
A1 Gea Beunders
A1 Jiddeke van de Kamp
A1 Pradeep Vasudevan
A1 Jenny Morton
A1 Katrien Smets
A1 Tjitske Kleefstra
A1 Sonja A de Munnik
A1 Janneke Schuurs-Hoeijmakers
A1 Berten Ceulemans
A1 Marcella Zollino
A1 Sabine Hoffjan
A1 Stefan Wieczorek
A1 Joyce So
A1 Leanne Mercer
A1 Tanya Walker
A1 Lea Velsher
A1 the DDD study
A1 Michael J Parker
A1 Alex C Magee
A1 Bart Elffers
A1 R Frank Kooy
A1 Helger G Yntema
A1 Elizabeth J Meijers-Heijboer
A1 Erik A Sistermans
YR 2016
UL http://jmg.bmj.com/content/53/8/523.abstract
AB 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.