TY - JOUR
T1 - A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype
AU - Beunders, Gea
AU - van de Kamp, Jiddeke
AU - Vasudevan, Pradeep
AU - Morton, Jenny
AU - Smets, Katrien
AU - Kleefstra, Tjitske
AU - de Munnik, Sonja A.
AU - Schuurs-Hoeijmakers, Janneke
AU - Ceulemans, Berten
AU - Zollino, Marcella
AU - Hoffjan, Sabine
AU - Wieczorek, Stefan
AU - So, Joyce
AU - Mercer, Leanne
AU - Walker, Tanya
AU - Velsher, Lea
AU - Parker, Michael J.
AU - Magee, Alex C.
AU - Elffers, Bart
AU - Frank Kooy, R.
AU - Yntema, Helger G.
AU - Meijers-Heijboer, Elizabeth J.
AU - Sistermans, Erik A.
AU - The DDD study, DDD study
PY - 2016/8/1
Y1 - 2016/8/1
N2 - 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 50 deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the fulllength 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.
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 50 deletions, which are often inherited. Deletions and other mutations causing haploinsufficiency of the fulllength 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.
UR - http://www.scopus.com/inward/record.url?scp=84964577579&partnerID=8YFLogxK
U2 - https://doi.org/10.1136/jmedgenet-2015-103601
DO - https://doi.org/10.1136/jmedgenet-2015-103601
M3 - Article
C2 - 27075013
SN - 0022-2593
VL - 53
SP - 523
EP - 532
JO - Journal of medical genetics
JF - Journal of medical genetics
IS - 8
ER -