Fragile X syndrome (FXS), the most common monogenic cause of intellectual disability and autism spectrum disorder, has been one of the first neurodevelopmental disorders in which molecular and neuronal mechanisms of disease were identified, leading to the concept of targeting the underlying disease to reverse symptoms. Translating findings in basic science and animal models to humans with FXS has proven difficult. These challenges have prompted the FXS field to organize to build interlocking projects and initiatives to improve consistency of supportive care, make clinical research accessible to families, generate collaborative research on natural history, outcome measures and biomarkers, and create clinical trial consortia and novel trial designs. This work has resulted in improved success in recent clinical trials, providing key steps toward regulatory approval of disease-targeted treatments for FXS. Progress in the FXS field has informed translation of transformative new disease-targeted therapies for other monogenic neurodevelopmental disorders.

脆性 X 综合征 (FXS) 是智力残疾和自闭症谱系障碍最常见的单基因原因，是最早发现疾病的分子和神经元机制的神经发育障碍之一，导致了针对潜在疾病逆转的概念症状。事实证明，使用 FXS 将基础科学和动物模型中的发现转化为人类是很困难的。这些挑战促使 FXS 领域组织建立联锁项目和倡议，以提高支持性护理的一致性，使临床研究为家庭所用，在自然史、结果测量和生物标志物方面开展合作研究，并创建临床试验联盟和新颖的试验设计. 这项工作在最近的临床试验中取得了更大的成功，为 FXS 疾病靶向治疗的监管批准提供关键步骤。FXS 领域的进展为其他单基因神经发育障碍的变革性新疾病靶向疗法的转化提供了信息。