Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway
Autism spectrum disorder and other neurobehavioural comorbidities in rare disorders of the Ras/MAPK pathway
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DOI：
10.1111/dmcn.13394
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发表时间：
2017-05-01
影响因子：
3.8
通讯作者：
Green, Jonathan
中科院分区：
文献类型：
--
作者：
Garg, Shruti;Brooks, Ami;Green, Jonathan
目的调查 Ras/MAPK 通路罕见疾病（即 Noonan、心面皮肤 (CFC) 和 Costello 综合征）的认知和行为表型，特别是自闭症谱系障碍 (ASD) 和注意力缺陷多动障碍 (ADHD) 的患病率。方法通过区域遗传学服务和广告在 10 个月内招募了 50 名儿童。实施了一系列家长、儿童和观察措施，包括自闭症诊断面谈修订版和自闭症诊断观察量表。结果使用自闭症卓越标准合作项目，40 名努南综合征儿童中有 12 名 (30%) 表现出自闭症谱系障碍，40 名儿童中有 12 名 (30%) 具有部分自闭症特征，40 名儿童中有 16 名 (40%) 表现出非自闭症。努南综合征 ASD 组以男性为主，比例为 5:1。在 CFC 组中，九名儿童中有八名符合自闭症谱系障碍标准，性别分布相同。此外，Noonan 综合征组的 40 人中有 19 人（48%）和 CFC 组的 9 人中有 8 人（88.9%）的得分符合 ADHD 的临床标准。 Costello 综合征组中只有一个孩子。解释这是第一项表明 Noonan 和 CFC 综合征中 ASD 患病率较高的系统研究，因此提供了关键证据来支持 Ras/MAPK 通路在 ASD 病因学中的重要性。局限性包括在此类罕见疾病研究中不可避免地存在抽样偏差的可能性。
AimTo investigate the cognitive and behavioural phenotype in rare disorders of the Ras/MAPK pathway, namely Noonan, cardiofaciocutaneous (CFC), and Costello syndromes, particularly prevalence of autism spectrum disorder (ASD) and attention-deficit-hyperactivity disorder (ADHD).MethodFifty children were recruited over 10 months through the regional genetics service and advertisements. A range of parent, child, and observational measures were administered including Autism Diagnostic Interview-Revised and Autism Diagnostic Observation Scale.ResultsUsing the Collaborative Programme for Excellence in Autism criteria, 12 out of 40 children with Noonan syndrome (30%) showed ASD, and 12 out of 40 (30%) with partial ASD features and 16 out of 40 (40%) showed non-ASD. The Noonan syndrome ASD group showed male dominance in a ratio of 5:1. In the CFC group, eight out of nine children met the criteria for ASD, with equal sex distribution. Additionally 19 out of 40 (48%) of the Noonan syndrome group and eight out of nine (88.9%) of the CFC group scored met clinical criteria for ADHD. Only one child was in the Costello syndrome group.InterpretationThis is the first systematic study to suggest a high prevalence of ASD in Noonan and CFC syndromes, and thus offers crucial evidence to support the importance of the Ras/MAPK pathway in the aetiology of ASD. Limitations include the inevitable possibility of a sampling bias in a rare disorder study of this kind.