A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype
A detailed clinical analysis of 13 patients with AUTS2 syndrome further delineates the phenotypic spectrum and underscores the behavioural phenotype
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DOI：
10.1136/jmedgenet-2015-103601
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发表时间：
2016-08-01
影响因子：
4
通讯作者：
Sistermans, Erik A.
中科院分区：
文献类型：
--
作者：
Beunders, Gea;van de Kamp, Jiddeke;Sistermans, Erik A.
背景AUTS 2综合征是由基因组重排、缺失、基因内重复或突变破坏AUTS 2引起的"智力残疾（ID）综合征"。到目前为止，50例AUTS 2综合征已被描述，但临床数据是有限的，几乎所有的情况下涉及年幼的children. Methods我们提出了一个详细的临床描述13例（包括6名成人）与AUTS 2综合征谁有致病性突变或缺失的AUTS 2。结果所有患者均为边缘性至重度ID/发育迟缓，83 - 100%有小头畸形和喂养困难。先天性畸形是罕见的，但轻微的心脏缺陷，挛缩和生殖器畸形确实发生。成年人没有重大的健康问题;其中年龄最大的现在59岁。行为的特点是它是一个友好的外向的社会交往。自闭症的具体特征（如强迫行为）经常出现（83%），但经典自闭症没有被诊断为任何自闭症。轻度临床表型与小的框内50缺失相关，这通常是遗传的。缺失和其他突变造成单倍不足的全长AUTS2转录给一个更严重的表型和发生de novo.Conclusions独特的致病性缺失分散在AUTS2基因座周围的13例AUTS2综合征证实了表型基因型相关性。尽管存在个体差异，但AUTS 2综合征作为一种特定的ID综合征出现，具有小头畸形、进食困难、畸形特征和特定的行为表型。
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 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.