Age and ASD symptoms in Costello syndrome.
Age and ASD symptoms in Costello syndrome.
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Costello 综合征的年龄和 ASD 症状。
DOI：
10.1002/ajmg.a.38641
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发表时间：
2018
期刊：
影响因子：
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通讯作者：
Rauen,KatherineA
中科院分区：
文献类型：
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作者：
Young,Olivia;Perati,Shriya;Weiss,LaurenA;Rauen,KatherineA
Costello综合征（CS）是一种由ras/MAPK通路中HRAS基因突变引起的RASopathy，此前被认为与自闭症谱系障碍（ASD）的风险增加有关（Alfieri P et al., 2014; Adviento B et al., 2014; Garg S et al., 2017）。然而，最近一篇论文《Costello综合征儿童和青少年自闭症谱系障碍症状患病率的年龄相关差异》（Schwartz et al., 2017）的作者发现，4岁以上的CS受试者中没有ASD症状。在他们的研究中，Schwartz等人发现，在他们的14名CS受试者样本中，只有4岁及以下的儿童患ASD的比例显著升高，并最终得出结论：“CS个体在儿童早期可能由于严重的喂养和矫形问题而出现自闭症谱系，这些问题在4岁时得到改善，这表明这些儿童中的许多人最终可能会摆脱ASD的表现。”我们注意到Schwartz等人的研究设计中的几个元素可能影响了其结果和作者的结论。首先，正如作者指出的那样，他们的样本量是14个人（7个在年龄≤4岁的年龄组，7个在年龄较大的年龄组）。由于先前报道的CS患者出现显著ASD症状的频率约为（26-44）%(Adviento B et al., 2014; Alfieri P et al., 2014)，因此只有少数个体（~ 4-6）可能具有临床相关的ASD特征（与他们观察到的5/14一致），并且偶然落入两个年龄组中的一个年龄组的可能性不容忽视。在ASD按年龄均匀分布的情况下，他们的结果分别为5/7和0/7，与预期的2.5/7没有显著差异（P> 0.1）。其次，作者使用不同的问卷来评估年轻人和老年人的ASD，从而混淆了年龄和使用的ASD评估方法。第三，Schwartz等人在幼儿自闭症修正清单（M-CHAT）问卷中使用了宽松的阈值，正如他们报告的那样，只有两个CS个体符合更保守的阈值，在这种情况下，年龄组之间也没有显著差异。他们在老年组中使用了社会沟通问卷（SCQ）的标准阈值，类似于之前对CS和ASD的研究。
Costello syndrome (CS), a RASopathy caused by a mutation in the HRAS gene in the ras/MAPK pathway, has previously been associated with increased risk of autism spectrum disorder (ASD)(Alfieri P et al., 2014; Adviento B et al., 2014; Garg S et al., 2017). However, authors of a recent paper, Age Related Differences in Prevalence of Autism Spectrum Disorder Symptoms in Children and Adolescents with Costello Syndrome (Schwartz et al., 2017) found no ASD symptoms in CS subjects over age 4. In their study, Schwartz et al found significantly elevated rates of ASD only in children 4 years old and younger in their sample of 14 CS subjects, and ultimately concluded that “CS individuals may appear to fall on the autism spectrum in early childhood due to severe feeding and orthopedic problems that improve by age four, suggesting many of these children may eventually emerge out of an ASD presentation.” We noticed several elements of the design of Schwartz et al’s study that may have influenced its results and the authors’ conclusions. First, as the authors point out, their sample size is 14 individuals (7 in their young≤ 4y group, 7 in the older group). As the previously reported frequency of notable ASD symptoms in CS patients is approximately (26–44)%(Adviento B et al., 2014; Alfieri P et al., 2014), only a small number of individuals (~ 4–6) would be expected to have clinically relevant ASD traits (consistent with their observed 5/14) and the likelihood of falling by chance into only one of two age groups is not negligible. Neither their result of 5/7 in the young group nor 0/7 in the old group are significantly different than the expected 2.5/7 in each group if ASD were evenly distributed by age (P> 0.1). Second, the authors used different questionnaires to assess ASD in the younger and older groups, thus confounding age with the method of ASD-assessment used. Third, Schwartz et al used a lenient threshold in the Modified Checklist for Autism in Toddlers (M-CHAT) questionnaire for their younger age group, and as they report, only two CS individuals met the more conservative threshold–in which case there would also be no significant difference by age group. They used a standard threshold for Social Communication Questionnaire (SCQ) in the older group, similar to the previous studies of CS and ASD.