XYY 综合征青少年孤独症谱系障碍及神经发育特征分析。
Characterization of autism spectrum disorder and neurodevelopmental profiles in youth with XYY syndrome.
机构信息
Office of the Clinical Director, National Institute of Mental Health, National Institute of Health, Bethesda, MD, USA.
Developmental Neurogenomics Unit, Human Genetics Branch, National Institute of Mental Health, National Institutes of Health, Bethesda, MD, USA.
出版信息
J Neurodev Disord. 2018 Oct 22;10(1):30. doi: 10.1186/s11689-018-9248-7.
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."
背景
XYY 综合征是一种性染色体非整倍体，约每 850 名男婴中就有 1 名发生，与神经发育困难的风险增加有关。然而，XYY 患者的神经发育损伤特征，包括自闭症谱系障碍（ASD）的症状，仍知之甚少。这种知识上的差距在一定程度上持续存在，部分原因是缺乏具有密集和同质表型数据的患者队列。
方法
我们使用涵盖发育里程碑、智商、适应行为、学业成绩、行为问题和 ASD 的金标准诊断工具的标准化认知和行为评估工具，评估了一个位于单一中心的 64 名 XYY 患者队列，年龄在 5-25 岁之间。我们的目标是：（i）详细描述 XYY 的神经发育特征，重点关注 ASD 的诊断率和症状特征；（ii）通过对比产前和产后诊断的 XYY 亚组，筛选表型是否存在潜在的确定偏倚效应；（iii）使用图论分析定义表型变异的主要模块。
结果
尽管存在明显的个体间差异，但平均特征是发育延迟，智商和适应行为下降。语言和社交沟通功能受损最明显。ASD 的发病率为 14%，这些个体表现出的自闭症症状特征与没有 XYY 的 ASD 相似。与产后诊断个体相比，大多数神经发育维度在产前诊断个体中表现出较轻的损伤，在言语智商方面存在有临床意义的差异。特征网络分析显示三个可分离的模块，包括（i）认知和学业成绩，（ii）广泛的领域精神病理学和适应行为，以及（iii）与 ASD 相关的特征。
结论
通过更细致地了解 XYY 中的神经发育困难，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，激励提供更多的专门多学科支持，并为未来将 XYY 的行为表型与神经生物学结合起来的努力提供信息。
试验注册
ClinicalTrials.gov NCT00001246，“89-M-0006：儿童期发病精神障碍、内分泌障碍和健康对照的脑成像。”
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