BACKGROUND XYY syndrome is a sex chromosome aneuploidy that occurs in ~ 1/850 male births and is associated with increased risk for neurodevelopmental difficulties. However, the profile of neurodevelopmental impairments, including symptoms of autism spectrum disorder (ASD) in XYY remains poorly understood. This gap in knowledge has persisted in part due to lack of access to patient cohorts with dense and homogeneous phenotypic data. METHODS We evaluated a single-center cohort of 64 individuals with XYY aged 5-25 years, using a standardized battery of cognitive and behavioral assessments spanning developmental milestones, IQ, adaptive behavior, academic achievement, behavioral problems, and gold-standard diagnostic instruments for ASD. Our goals were to (i) detail the neurodevelopmental profile of XYY with a focus on ASD diagnostic rates and symptom profiles, (ii) screen phenotypes for potential ascertainment bias effects by contrasting pre- vs. postnatally diagnosed XYY subgroups, and (iii) define major modules of phenotypic variation using graph-theoretical analysis. RESULTS Although there was marked inter-individual variability, the average profile was characterized by some degree of developmental delay, and decreased IQ and adaptive behavior. Impairments were most pronounced for language and socio-communicative functioning. The rate of ASD was 14%, and these individuals exhibited autism symptom profiles resembling those observed in ASD without XYY. Most neurodevelopmental dimensions showed milder impairment among pre- vs. postnatally diagnosed individuals, with clinically meaningful differences in verbal IQ. Feature network analysis revealed three reliably separable modules comprising (i) cognition and academic achievement, (ii) broad domain psychopathology and adaptive behavior, and (iii) ASD-related features. CONCLUSIONS By adding granularity to our understanding of neurodevelopmental difficulties in XYY, these findings assist targeted clinical assessment of newly identified cases, motivate greater provision of specialized multidisciplinary support, and inform future efforts to integrate behavioral phenotypes in XYY with neurobiology. TRIAL REGISTRATIONS ClinicalTrials.gov NCT00001246 , "89-M-0006: Brain Imaging of Childhood Onset Psychiatric Disorders, Endocrine Disorders and Healthy Controls."

中文翻译：

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XYY 综合征青少年自闭症谱系障碍和神经发育特征的特征。

背景 XYY 综合征是一种性染色体非整倍体，约 1/850 的男性新生儿发生这种情况，并且与神经发育困难的风险增加相关。然而，人们对 XYY 神经发育障碍（包括自闭症谱系障碍 (ASD) 症状）的概况仍知之甚少。这种知识差距一直存在，部分原因是无法获得具有密集且同质表型数据的患者群体。方法 我们评估了 64 名 5-25 岁 XYY 个体的单中心队列，使用一套标准化的认知和行为评估，涵盖发育里程碑、智商、适应性行为、学业成就、行为问题和黄金标准诊断仪器自闭症谱系障碍。我们的目标是 (i) 详细介绍 XYY 的神经发育概况，重点关注 ASD 诊断率和症状概况，(ii) 通过对比产前与产后诊断的 XYY 亚组来筛选表型是否存在潜在的确定偏倚效应，以及 (iii) 定义使用图论分析的表型变异的主要模块。结果 尽管存在明显的个体差异，但平均特征是一定程度的发育迟缓、智商和适应性行为下降。语言和社会交流功能的障碍最为明显。自闭症谱系障碍的发生率为 14%，这些人表现出的自闭症症状特征与在没有 XYY 的自闭症谱系障碍中观察到的相似。大多数神经发育维度在产前诊断的个体与产后诊断的个体中表现出较轻微的损害，并且在言语智商方面存在具有临床意义的差异。特征网络分析揭示了三个可靠分离的模块，包括（i）认知和学术成就，（ii）广泛的精神病理学和适应性行为，以及（iii）自闭症谱系障碍相关特征。结论 通过增加我们对 XYY 神经发育困难的理解，这些发现有助于对新发现的病例进行有针对性的临床评估，激励更多地提供专门的多学科支持，并为未来将 XYY 行为表型与神经生物学整合的努力提供信息。试验注册 ClinicalTrials.gov NCT00001246，“89-M-0006：儿童期发病的精神疾病、内分泌疾病和健康控制的脑成像。”