Fragile X syndrome (FXS) is a neurodevelopmental disorder that causes intellectual disability. It is a leading known genetic cause of autism. In addition to cognitive, social, and communication deficits, humans with FXS demonstrate abnormal sensory processing including sensory hypersensitivity. Sensory hypersensitivity commonly manifests as auditory, tactile, or visual defensiveness or avoidance. Clinical, behavioral, and electrophysiological studies consistently show auditory hypersensitivity, impaired habituation to repeated sounds, and reduced auditory attention in humans with FXS. Children with FXS also exhibit significant visuospatial impairments. Studies in infants and toddlers with FXS have documented impairments in processing texture-defined motion stimuli, temporal flicker, perceiving ordinal numerical sequence, and the ability to maintain the identity of dynamic object information during occlusion. Consistent with the observations in humans with FXS, fragile X mental retardation 1 ( Fmr1) gene knockout (KO) rodent models of FXS also show seizures, abnormal visual-evoked responses, auditory hypersensitivity, and abnormal processing at multiple levels of the auditory system, including altered acoustic startle responses. Among other sensory symptoms, individuals with FXS exhibit tactile defensiveness. Fmr1 KO mice also show impaired encoding of tactile stimulation frequency and larger size of receptive fields in the somatosensory cortex. Since sensory deficits are relatively more tractable from circuit mechanisms and developmental perspectives than more complex social behaviors, the focus of this review is on clinical, functional, and structural studies that outline the auditory, visual, and somatosensory processing deficits in FXS. The similarities in sensory phenotypes between humans with FXS and animal models suggest a likely conservation of basic sensory processing circuits across species and may provide a translational platform to not just develop biomarkers but also to understand underlying mechanisms. We argue that preclinical studies in animal models of FXS can facilitate the ongoing search for new therapeutic approaches in FXS by understanding mechanisms of basic sensory processing circuits and behaviors that are conserved across species.

中文翻译：

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易碎X综合征的感觉处理表型。

脆弱X综合征（FXS）是导致智力残疾的神经发育障碍。它是自闭症的已知的主要遗传原因。除了认知，社交和沟通方面的缺陷外，患有FXS的人还表现出异常的感觉处理，包括感觉超敏反应。感觉超敏反应通常表现为听觉，触觉或视觉防御或回避。临床，行为和电生理研究始终显示，FXS人体的听觉过敏，对重复声音的习惯受损以及听觉注意力降低。患有FXS的儿童也表现出明显的视觉空间障碍。对FXS婴儿进行的研究表明，在处理纹理定义的运动刺激，时间闪烁，感知序数序列，以及在遮挡过程中保持动态对象信息身份的能力。与在FXS人类中观察到的结果一致，FXS的脆弱X智力低下1（Fmr1）基因敲除（KO）啮齿动物模型还显示出癫痫发作，异常视觉诱发反应，听觉超敏反应以及听觉系统在多个层次上的异常处理，包括改变的听觉惊吓反应。在其他感觉症状中，具有FXS的个体表现出触觉防御能力。Fmr1 KO小鼠还显示出触觉刺激频率的编码受损以及体感皮层中较大的感受野大小。由于从电路机制和发展的角度来看，感觉缺陷相对比更复杂的社会行为更容易解决，因此，本文的重点是临床，功能，结构研究概述了FXS的听觉，视觉和躯体感觉处理缺陷。具有FXS的人类与动物模型之间在感觉表型上的相似性表明，可能在物种间保留了基本的感觉处理电路，并且可能提供一个翻译平台，不仅可以开发生物标记，而且可以了解潜在的机制。我们认为，在FXS动物模型中进行临床前研究可以通过了解基本的感觉处理电路的机制和跨物种保守的行为，来促进FXS的新治疗方法的持续搜索。具有FXS的人类与动物模型之间在感觉表型上的相似性表明，可能在物种间保留了基本的感觉处理电路，并且可能提供一个翻译平台，不仅可以开发生物标记，而且可以了解潜在的机制。我们认为，在FXS动物模型中进行临床前研究可以通过了解基本的感觉处理电路的机制和跨物种保守的行为，来促进FXS的新治疗方法的持续搜索。具有FXS的人类与动物模型之间在感觉表型上的相似性表明，可能在物种间保留了基本的感觉处理电路，并且可能提供一个翻译平台，不仅可以开发生物标记，而且可以了解潜在的机制。我们认为，在FXS动物模型中进行临床前研究可以通过了解基本的感觉处理电路的机制和跨物种保守的行为，来促进FXS的新治疗方法的持续搜索。