A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype

Gea Beunders, Jiddeke van de Kamp, Pradeep Vasudevan, Jenny Morton, Katrien Smets, Tjitske Kleefstra, Sonja A. de Munnik, Janneke Schuurs-Hoeijmakers, Berten Ceulemans, Marcella Zollino, Sabine Hoffjan, Stefan Wieczorek, Joyce So, Leanne Mercer, Tanya Walker, Lea Velsher, Michael J. Parker, Alex C. Magee, Bart Elffers, R. Frank Kooy & 4 others Helger G. Yntema, Elizabeth J. Meijers-Heijboer, Erik A. Sistermans, DDD study The DDD study

Research output: Contribution to journalArticleAcademicpeer-review

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 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.

Original languageEnglish
Pages (from-to)523-532
Number of pages10
JournalJournal of Medical Genetics
Volume53
Issue number8
DOIs
Publication statusPublished - 1 Aug 2016

Cite this

Beunders, Gea ; van de Kamp, Jiddeke ; Vasudevan, Pradeep ; Morton, Jenny ; Smets, Katrien ; Kleefstra, Tjitske ; de Munnik, Sonja A. ; Schuurs-Hoeijmakers, Janneke ; Ceulemans, Berten ; Zollino, Marcella ; Hoffjan, Sabine ; Wieczorek, Stefan ; So, Joyce ; Mercer, Leanne ; Walker, Tanya ; Velsher, Lea ; Parker, Michael J. ; Magee, Alex C. ; Elffers, Bart ; Frank Kooy, R. ; Yntema, Helger G. ; Meijers-Heijboer, Elizabeth J. ; Sistermans, Erik A. ; The DDD study, DDD study. / A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype. In: Journal of Medical Genetics. 2016 ; Vol. 53, No. 8. pp. 523-532.
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title = "A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype",
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 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.",
author = "Gea Beunders and {van de Kamp}, Jiddeke and Pradeep Vasudevan and Jenny Morton and Katrien Smets and Tjitske Kleefstra and {de Munnik}, {Sonja A.} and Janneke Schuurs-Hoeijmakers and Berten Ceulemans and Marcella Zollino and Sabine Hoffjan and Stefan Wieczorek and Joyce So and Leanne Mercer and Tanya Walker and Lea Velsher and Parker, {Michael J.} and Magee, {Alex C.} and Bart Elffers and {Frank Kooy}, R. and Yntema, {Helger G.} and Meijers-Heijboer, {Elizabeth J.} and Sistermans, {Erik A.} and {The DDD study}, {DDD study}",
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language = "English",
volume = "53",
pages = "523--532",
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Beunders, G, van de Kamp, J, Vasudevan, P, Morton, J, Smets, K, Kleefstra, T, de Munnik, SA, Schuurs-Hoeijmakers, J, Ceulemans, B, Zollino, M, Hoffjan, S, Wieczorek, S, So, J, Mercer, L, Walker, T, Velsher, L, Parker, MJ, Magee, AC, Elffers, B, Frank Kooy, R, Yntema, HG, Meijers-Heijboer, EJ, Sistermans, EA & The DDD study, DDDS 2016, 'A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype' Journal of Medical Genetics, vol. 53, no. 8, pp. 523-532. https://doi.org/10.1136/jmedgenet-2015-103601

A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype. / Beunders, Gea; van de Kamp, Jiddeke; Vasudevan, Pradeep; Morton, Jenny; Smets, Katrien; Kleefstra, Tjitske; de Munnik, Sonja A.; Schuurs-Hoeijmakers, Janneke; Ceulemans, Berten; Zollino, Marcella; Hoffjan, Sabine; Wieczorek, Stefan; So, Joyce; Mercer, Leanne; Walker, Tanya; Velsher, Lea; Parker, Michael J.; Magee, Alex C.; Elffers, Bart; Frank Kooy, R.; Yntema, Helger G.; Meijers-Heijboer, Elizabeth J.; Sistermans, Erik A.; The DDD study, DDD study.

In: Journal of Medical Genetics, Vol. 53, No. 8, 01.08.2016, p. 523-532.

Research output: Contribution to journalArticleAcademicpeer-review

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 - 10.1136/jmedgenet-2015-103601

DO - 10.1136/jmedgenet-2015-103601

M3 - Article

VL - 53

SP - 523

EP - 532

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 8

ER -