BackgroundRASopathies are associated with an increased risk of autism spectrum disorder (ASD). For neurofibromatosis type 1 (NF1) there is ample evidence for this increased risk, while for other RASopathies this association has been studied less. No specific ASD profile has been delineated so far for RASopathies or a specific RASopathy individually.MethodsWe conducted a systematic review to investigate whether a specific RASopathy is associated with a specific ASD profile, or if RASopathies altogether have a distinct ASD profile compared to idiopathic ASD (iASD). We searched PubMed, Web of Science, and Open Grey for data about ASD features in RASopathies and potential modifiers.ResultsWe included 41 articles on ASD features in NF1, Noonan syndrome (NS), Costello syndrome (CS), and cardio‐facio‐cutaneous syndrome (CFC). Individuals with NF1, NS, CS, and CFC on average have higher ASD symptomatology than healthy controls and unaffected siblings, though less than people with iASD. There is insufficient evidence for a distinct ASD phenotype in RASopathies compared to iASD or when RASopathies are compared with each other. We identified several potentially modifying factors of ASD symptoms in RASopathies.ConclusionsOur systematic review found no convincing evidence for a specific ASD profile in RASopathies compared to iASD, or in a specific RASopathy compared to other RASopathies. However, we identified important limitations in the research literature which may also account for this result. These limitations are discussed and recommendations for future research are formulated.

中文翻译：

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RASopathies 中的自闭症谱系障碍概况：系统评价

背景RASopathies 与自闭症谱系障碍（ASD）风险增加相关。对于 1 型神经纤维瘤病 (NF1)，有充分的证据表明这种风险增加，而对于其他 RASo 病，这种关联的研究较少。到目前为止，还没有针对 RASopathies 或单独的特定 RASopathies 描述出特定的 ASD 特征。方法我们进行了系统评价，以调查特定 RASopathies 是否与特定的 ASD 特征相关，或者与特发性 ASD 相比，RASopathies 是否总共具有独特的 ASD 特征（ iASD）。我们搜索了 PubMed、Web of Science 和 Open Gray，以获取有关 RASopathies 中 ASD 特征和潜在修饰因素的数据。结果我们纳入了 41 篇关于 NF1、Noonan 综合征 (NS)、Costello 综合征 (CS) 和心面皮肤 ASD 特征的文章综合症（CFC）。患有 NF1、NS、CS 和 CFC 的个体平均比健康对照者和未受影响的兄弟姐妹具有更高的 ASD 症状，但低于 iASD 患者。没有足够的证据表明 RASopathies 与 iASD 相比或 RASopathies 相互比较时具有不同的 ASD 表型。我们确定了 RASopathies 中 ASD 症状的几个潜在改变因素。结论我们的系统评价没有发现令人信服的证据表明 RASopathies 与 iASD 相比的特定 ASD 特征，或与其他 RASopathies 相比的特定 RASopathies。然而，我们发现研究文献中存在重要的局限性，这也可能解释了这一结果。讨论了这些局限性并制定了未来研究的建议。