Natali Bozhilova, Alice Welham, Dawn Adams, Stacey Bissell, Hilgo Bruining, Hayley Crawford, Kate Eden, Lisa Nelson, Christopher Oliver, Laurie Powis, Caroline Richards, Jane Waite, Peter Watson, Hefin Rhys, Lucy Wilde, Kate Woodcock, Joanna Moss
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引用次数: 0
Abstract
Background: Phenotypic studies have identified distinct patterns of autistic characteristics in genetic syndromes associated with intellectual disability (ID), leading to diagnostic uncertainty and compromised access to autism-related support. Previous research has tended to include small samples and diverse measures, which limits the generalisability of findings. In this study, we generated detailed profiles of autistic characteristics in a large sample of > 1500 individuals with rare genetic syndromes.
Methods: Profiles of autistic characteristics based on the Social Communication Questionnaire (SCQ) scores were generated for thirteen genetic syndrome groups (Angelman n = 154, Cri du Chat n = 75, Cornelia de Lange n = 199, fragile X n = 297, Prader-Willi n = 278, Lowe n = 89, Smith-Magenis n = 54, Down n = 135, Sotos n = 40, Rubinstein-Taybi n = 102, 1p36 deletion n = 41, tuberous sclerosis complex n = 83 and Phelan-McDermid n = 35 syndromes). It was hypothesised that each syndrome group would evidence a degree of specificity in autistic characteristics. To test this hypothesis, a classification algorithm via support vector machine (SVM) learning was applied to scores from over 1500 individuals diagnosed with one of the thirteen genetic syndromes and autistic individuals who did not have a known genetic syndrome (ASD; n = 254). Self-help skills were included as an additional predictor.
Results: Genetic syndromes were associated with different but overlapping autism-related profiles, indicated by the substantial accuracy of the entire, multiclass SVM model (55% correctly classified individuals). Syndrome groups such as Angelman, fragile X, Prader-Willi, Rubinstein-Taybi and Cornelia de Lange showed greater phenotypic specificity than groups such as Cri du Chat, Lowe, Smith-Magenis, tuberous sclerosis complex, Sotos and Phelan-McDermid. The inclusion of the ASD reference group and self-help skills did not change the model accuracy.
Limitations: The key limitations of our study include a cross-sectional design, reliance on a screening tool which focuses primarily on social communication skills and imbalanced sample size across syndrome groups.
Conclusions: These findings replicate and extend previous work, demonstrating syndrome-specific profiles of autistic characteristics in people with genetic syndromes compared to autistic individuals without a genetic syndrome. This work calls for greater precision of assessment of autistic characteristics in individuals with genetic syndromes associated with ID.
背景:表型研究发现,在与智力障碍(ID)相关的遗传综合征中,自闭症的特征具有不同的模式,这导致了诊断的不确定性,并影响了自闭症相关支持的获得。以往的研究往往采用小样本和不同的测量方法,这限制了研究结果的普遍性。在这项研究中,我们在超过 1500 名罕见遗传综合征患者的大样本中生成了详细的自闭症特征图谱:方法:根据社会交往问卷(SCQ)得分,为 13 个遗传综合征群体(安杰尔曼 n = 154、Cri du Chat n = 75、科妮莉亚-德-朗格 n = 199、脆性 X n = 297、普拉德-威利 n = 27)生成自闭症特征图谱、普拉德-威利综合征 n = 278、洛氏综合征 n = 89、史密斯-马盖尼斯综合征 n = 54、唐氏综合征 n = 135、索托斯综合征 n = 40、鲁宾斯坦-泰比综合征 n = 102、1p36 缺失综合征 n = 41、结节性硬化综合征 n = 83 和菲兰-麦克德米综合征 n = 35)。假设每个综合征组在自闭症特征方面都有一定程度的特异性。为了验证这一假设,通过支持向量机(SVM)学习对超过 1500 名被诊断患有十三种遗传综合征之一的患者和未患有已知遗传综合征的自闭症患者(ASD;n = 254)的得分进行了分类。自助技能被列为额外的预测指标:结果:遗传综合征与不同但重叠的自闭症相关特征有关,整个多分类 SVM 模型的准确率很高(55% 的个体被正确分类)。与 Cri du Chat、Lowe、Smith-Magenis、结节性硬化综合征、Sotos 和 Phelan-McDermid 等综合征组相比,Angelman、脆性 X、Prader-Willi、Rubinstein-Taybi 和 Cornelia de Lange 等综合征组显示出更大的表型特异性。加入ASD参照组和自助技能并没有改变模型的准确性:我们研究的主要局限性包括:横断面设计、依赖于主要侧重于社会交流能力的筛查工具,以及各综合征群体的样本量不平衡:这些研究结果重复并扩展了之前的工作,表明与无遗传综合征的自闭症患者相比,遗传综合征患者的自闭症特征具有综合征特异性。这项工作要求对与智障相关的遗传综合征患者的自闭症特征进行更精确的评估。
期刊介绍:
Molecular Autism is a peer-reviewed, open access journal that publishes high-quality basic, translational and clinical research that has relevance to the etiology, pathobiology, or treatment of autism and related neurodevelopmental conditions. Research that includes integration across levels is encouraged. Molecular Autism publishes empirical studies, reviews, and brief communications.