Emergence and Stability of Autism in Fragile X Syndrome

描述（由申请人提供）：自闭症是一种破坏性和常见的发育障碍，也是一个主要的公共卫生问题。在高危婴儿中早期发现自闭症对这些儿童、他们的家庭和支持他们的系统至关重要。脆性X染色体综合征（FXS）是自闭症的主要遗传原因，而FXS和FMR1预突变（FXpm）与自闭症高度相关。尽管自闭症与FMR1基因突变高度相关，但没有研究检测FXS或FXpm中自闭症的早期指标，也没有研究检测FX中早期自闭症指标对特发性（非FX）自闭症的特异性。本申请“脆性X综合征中自闭症的出现和稳定性”提出了一项纵向前瞻性研究，研究FXS和FXpm婴儿在9岁、12岁和24岁时的早期自闭症特征，并与有哥哥或姐姐诊断为自闭症的婴儿（以下简称“ASIBS”）和典型对照（TD）进行对比。该应用程序利用了最近的科学进展，包括识别生命最初2年的自闭症，FXS和fxpm -自闭症共发病的特征，以及发育神经科学的发现，以确定与早期出现的自闭症特征（例如，注意力）相关的潜在生理机制。这项工作将促进我们对两种重要健康状况：FX和自闭症的关键风险过渡期间自闭症特征进展的理解。在这个项目中，我们将使用一种综合的行为，包括标准化和实验室测量，以及生物标记方法，将自闭症行为作为一个连续体，而不是严格的诊断类别。

DESCRIPTION (provided by applicant): Autism is a devastating and common developmental disorder and a major public health concern. Early detection of autism in high risk infants is critical to these children, their families, and the systems that support them. Fragile X syndrome (FXS) is the leading genetic cause of autism, and both FXS and the FMR1 premutation (FXpm) are highly associated with autism. Despite the high association of autism and FMR1 gene mutations, no study has examined early indicators of autism in FXS or FXpm or examined specificity of early autism indicators in FX to idiopathic (non-FX) autism. This application "Emergence and Stability of Autism in Fragile X Syndrome" proposes a longitudinal prospective study of the early autism features in infants with FXS and FXpm at 9, 12, and 24 in contrast to infants with an older sibling diagnosed with autism (hereafter referred to as "ASIBS") and typical controls (TD). This application takes advantage of recent scientific advances in the identification of autism in the first 2 years of life, characterization of the FXS and FXpm-autism co-morbidity and findings from developmental neuroscience to identify underlying physiological mechanisms associated with early emerging autistic features (e.g., attention). This work will advance our understanding of the progression of autism features during the key risk transition period for two conditions of major health importance: FX and autism. In this project, we will use a combined behavioral, both standardized and laboratory measures, and biomarker approach focused on autistic behavior as a continuum rather than rigid diagnostic categories.