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脆性X综合征

Fragile X syndrome

ORPHA:908疾病中国目录 第2批 · 29

定义 英文原文（暂无中文）

A rare genetic disease associated with mild to severe intellectual deficit that may be associated with behavioral disorders and characteristic physical features including a high forehead, prominent and large ears, hyperextensible finger joints, flat feet with pronation and, in adolescent and adult males, macroorchidism.

别名

Martin-Bell综合征

基本事实

遗传方式
X 连锁显性
发病年龄
儿童期、婴儿期、新生儿期
患病率
1-5 / 10 000

相关基因 1

基因名称关联类型
FMR1fragile X messenger ribonucleoprotein 1Disease-causing germline mutation(s) (loss of function) in

临床表型 33

极常见 99–80%7

  • 异常言语模式 HP:0002167
  • 慢性中耳炎 HP:0000389
  • 叶酸依赖性Xq28脆性位点 HP:0003564
  • 中度智力障碍 HP:0002342
  • 关节过度活动 HP:0001382
  • 巨睾 HP:0000053
  • 扁平足 HP:0001763

常见 79–30%17

  • 注意力缺陷多动障碍 HP:0007018
  • 粗大运动发育迟缓 HP:0002194
  • 语言发育迟缓 HP:0000750
  • 前额突出 HP:0002007
  • 胃食管反流 HP:0002020
  • 肌张力减退 HP:0001252
  • 大额头 HP:0002003
  • 长脸 HP:0000276
  • 巨头畸形 HP:0000256
  • 巨耳畸形 HP:0000400
  • 下颌前突 HP:0000303
  • 脸狭窄 HP:0000275
  • 中耳炎 HP:0000388
  • 招风耳 HP:0000411
  • 脊柱侧弯 HP:0002650
  • 鼻窦炎 HP:0000246
  • 睡眠异常 HP:0002360

偶见 29–5%9

  • 焦虑 HP:0000739
  • 生主动脉动脉瘤 HP:0004970
  • 孤独症 HP:0000717
  • 大脑皮层萎缩 HP:0002120
  • 易激惹 HP:0000737
  • 二尖瓣脱垂 HP:0001634
  • 癫痫发作 HP:0001250
  • 自伤行为 HP:0100716
  • 斜视 HP:0000486

近两年的全球研究 2,275L2

2024/10 起在 Europe PMC 检索所得，按发表时间倒序显示最近 20 篇。标题未译成中文——自动翻译需要接入 LLM 服务，尚未引入。

  • 2026-10综述
    Preimplantation Genetic Testing for FMR1 CGG Repeat Expansions: Clinical and Molecular Aspects in Assisted Reproduction
    JBRA assisted reproduction · DOI · Europe PMC
  • 2026-10开放获取
    Preparing Genetic Counselors for Advocacy Partnerships: A Novel Internship Model
    Journal of genetic counseling · DOI · Europe PMC
  • 2026-10
    Decision-Making in IVF: Restrictions on PGT-M Positive Embryo Transfers-A Qualitative Study
    Journal of genetic counseling · DOI · Europe PMC
  • 2026-10
    Decision-Making Around Preimplantation Genetic Testing by Individuals With Neurofibromatosis Type I: A Qualitative Study
    Journal of genetic counseling · DOI · Europe PMC
  • 2026-09
    FMRP Regulates NrCAM Expression via β-catenin and Modulates PSD95, Dendritic Spines and Autism-like Behaviors
    Neuroscience bulletin · DOI · Europe PMC
  • 2026-09
    Aberrant Neural Outputs and Disrupted Neural Oscillations of the Cerebellar Nuclei in a Mouse Model of Fragile X Syndrome
    Neuroscience bulletin · DOI · Europe PMC
  • 2026-09开放获取
    <i>TRAF7</i> mutations stabilize K/NRAS and hyperactivate MAPK signaling to cause CAFDADD neurodevelopmental defects
    Science advances · DOI · Europe PMC
  • 2026-09开放获取
    Memory, attention, and executive function in intellectual and developmental disabilities
    Journal of neurodevelopmental disorders · DOI · Europe PMC
  • 2026-09
    Initial Review of Government-Funded Reproductive Carrier Screening for Cystic Fibrosis, Spinal Muscular Atrophy and Fragile X Syndrome
    Prenatal diagnosis · DOI · Europe PMC
  • 2026-09病例报告
    Spontaneous Coronary Artery Dissection in Fragile X Syndrome: A Novel IVUS-Guided PCI Approach
    JACC. Case reports · DOI · Europe PMC
  • 2026-09荟萃分析综述开放获取
    Rapid Review of the Brief Observation of Social Communication Change (BOSCC) Shows It Can Detect Behavioural Changes in Social Communication in Autism
    Autism : the international journal of research and practice · DOI · Europe PMC
  • 2026-09开放获取
    Beyond Words: Natural Language Sampling of Lexical and Non-Word Vocalizations in Preschool Children with Autism, Down Syndrome, and Fragile X Syndrome
    medRxiv
  • 2026-09综述开放获取
    Retinoic acid in health and disease
    Signal transduction and targeted therapy · DOI · Europe PMC
  • 2026-09病例报告开放获取
    Fragile X-associated tremor/ataxia syndrome with autoimmune hepatitis requiring liver transplantation
    BMJ case reports · DOI · Europe PMC
  • 2026-09开放获取
    Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity
    eLife · DOI · Europe PMC
  • 2026-09
    A cell type-specific switch in GluN2D NMDA receptors drives cortical circuit hyperexcitability and sensory-driven cortical synchronization deficits in a Fragile X Syndrome model
    Biological psychiatry · DOI · Europe PMC
  • 2026-09综述
    Translational dysregulation as a mechanistic driver of cognitive, behavioral, and affective phenotypes in FXS and TSC
    Neuroscience and biobehavioral reviews · DOI · Europe PMC
  • 2026-09开放获取
    Human Neuronal Modeling of DLG4-Related Synaptopathy Reveals Network Dysfunction and Partial Rescue by Omega-3 Fatty Acid Docosahexaenoic Acid (DHA)
    Cells · DOI · Europe PMC
  • 2026-09开放获取
    Transcriptome of fetal cortex of tree shrew underlying the emergence of outer subventricular zone
    Communications biology · DOI · Europe PMC
  • 2026-09综述开放获取
    <i>Drosophila melanogaster</i> as a Model for Autism Spectrum Disorder: Insights into Lifelong Neuronal Vulnerability
    International journal of molecular sciences · DOI · Europe PMC

境外已获批用于本病的药物 0L2

欧盟与美国均未检索到已获批用于本病的药物。

尚未获批的在研药物（46 项）

这些药已被欧盟或美国的监管机构认定为罕见病用药（英文 orphan drug designation，中文行业里通称「孤儿药资格」——「孤儿」说的是这类药市场太小、没有厂商愿意认领，不是在说病人）。但这只是一种监管身份：意味着监管机构给予研发上的激励，不代表这个药已被证明有效，也不代表将来一定能上市，绝大多数最终不会成药。列在这里是为了看清有哪些方向正在被尝试。

  • R-baclofen欧盟2011-04-15
    Treatment of fragile X syndrome
    官方记录
  • acamprosate calcium欧盟2014-10-15
    Treatment of fragile X syndrome
    官方记录
  • Glycyl-L-2-methylprolyl-L-glutamic acid欧盟2015-07-28
    Treatment of fragile X syndrome
    官方记录
  • pyridoxine;l-pyroglutamic acid欧盟2016-06-27
    Treatment of fragile X syndrome
    官方记录
  • alpha-tocopherol;ascorbic acid欧盟2017-02-27
    Treatment of fragile X syndrome
    官方记录
  • cannabidivarin欧盟2018-02-22
    Treatment of fragile X syndrome
    官方记录
  • balipodect欧盟2019-04-14
    Treatment of fragile X syndrome
    官方记录
  • sulindac欧盟2020-12-09
    Treatment of fragile X syndrome
    官方记录
  • 2-[4-[3-(methylamino)-1-phenylpropoxy]phenyl]ethanol hydrochloride欧盟2021-05-20
    Treatment of fragile X syndrome
    官方记录
  • psilocybine欧盟2021-10-15
    Treatment of fragile X syndrome
    官方记录
  • cannabidiol欧盟2022-02-25
    Treatment of fragile X syndrome (FXS)
    官方记录
  • codergocrine mesilate;oxitriptan欧盟2022-03-16
    Treatment of fragile X syndrome
    官方记录
  • Ibudilast欧盟2022-05-16
    Treatment of fragile X syndrome
    官方记录
  • 5,5-dimethyl-3-[2-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl欧盟2023-03-20
    Treatment of fragile X syndrome
    官方记录
  • zatolmilast欧盟2024-03-21
    Treatment of fragile X syndrome
    官方记录
  • 3-chloro-4-fluorophenyl-(4-fluoro-4-(((5-methylpyrimidin-2-ylmethyl)am欧盟2024-11-11
    Treatment of fragile X syndrome
    官方记录
  • (R)-3-(5-dimethylcarbamoyl-pent-1-enyl)-N-(2-hydroxy-1methylethyl)benz欧盟
    Treatment of fragile X syndrome
    官方记录
  • guanfacine美国1999-08-05
    Treatment of fragile X syndrome.
    官方记录
  • Fenobam hydrochloride美国2006-11-20
    Treatment of fragile X syndrome
    官方记录
  • Valproate美国2008-05-05
    Treatment of fragile X syndrome
    官方记录
  • 3-fluoro-5-[5-(2-menthyl-thiazol-4-ylethylnyl)-pyridin-2-yl]-benzonitr美国2008-07-28
    Treatment of behavioral abnormalities associated with fragile X syndrome.
    官方记录
  • R-4-amino-3-(4-chlorophenyl)butanoic acid美国2008-11-28
    Treatment of the behavorial abnormalities associated with fragile X syndrome
    官方记录
  • (-)-(3aR,4S,7aR)-4-Hydroxy-4-m-tolylethynyl-octahydro-indole-1-carboxy美国2011-10-12
    Treatment of Fragile X syndrome
    官方记录
  • acamprosate美国2013-03-25
    Treatment of fragile X syndrome
    官方记录
  • Trofinetide美国2013-10-23
    Treatment of Fragile X Syndrome
    官方记录
  • metadoxine美国2013-12-16
    Treatment of Fragile X Syndrome
    官方记录
  • bryostatin 1美国2015-03-31
    Treatment of Fragile X Syndrome.
    官方记录
  • (3S)-(+)-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluorom美国2015-12-09
    Treatment of Fragile X Syndrome.
    官方记录
  • cannabidiol美国2016-02-23
    Treatment of Fragile X syndrome
    官方记录
  • ganaxolone美国2016-12-28
    Treatment of Fragile X Syndrome
    官方记录
  • Cannabidivarin美国2017-06-06
    Treatment of Fragile X syndrome
    官方记录
  • 5,5-dimethyl-3-[2-(7-methylspiro[2H-benzofuran-3,1'-cyclopropane]-4-yl美国2017-06-12
    Treatment of fragile X syndrome
    官方记录
  • Gaboxadol美国2017-10-03
    Treatment of Fragile X syndrome
    官方记录
  • zatolmilast美国2018-03-26
    Treatment of Fragile X Syndrome
    官方记录
  • alpha tocopherol and ascorbic acid美国2019-03-28
    Treatment of Fragile X syndrome
    官方记录
  • Sulindac美国2021-05-10
    Treatment of Fragile X syndrome
    官方记录
  • Psilocybin美国2021-10-25
    Treatment of Fragile X Syndrome
    官方记录
  • 4-(3-cyano-6-ethoxyquinolin-2-yl)-N- (2-fluorophenyl)-1,4-diazepane-1-美国2022-05-26
    Treatment of Fragile X syndrome (FXS)
    官方记录
  • Ibudilast美国2022-06-15
    Treatment of Fragile X syndrome
    官方记录
  • replication-incompetent adeno-associated virus serotype 9 vector encod美国2022-06-16
    Treatment of Fragile X Syndrome
    官方记录

另有 6 项未列出。

数据来自欧洲药品管理局（EMA）的药品与罕见病用药资格公开导出表，以及美国 FDA 的罕见病用药资格数据库（Orphan Drug Product Designation Database）。两边口径不同：欧盟一侧取的是当前状态仍为「已授权」的药品；美国一侧记录的是「曾获批准」这一事实，FDA 的公开表不追踪药物此后是否退市（例如 Relyvrio 于 2024 年撤市，表中仍记为已获批）。请以官方记录页为准。

在中国开展的临床试验 1L2

按病名在 ClinicalTrials.gov 检索、并校验研究中心含中国大陆而来。登记状态不等于现在真的能入组——务必按 NCT 号到原站核实，并与主治医生商量。

当前没有检索到登记为可入组的试验。

其他状态的试验（1 项）
  • 已完成NCT05120505
    Metformin in Children With Fragile X Syndrome
    IV 期 · 干预性 · 2021/12/29Children's Hospital of Fudan University
    中国研究中心 1 个：Shanghai

中国境外的在招试验 19L2

这些试验在中国没有研究中心，通常无法直接报名——入组一般要求在当地居住并接受随访。列在这里是因为它另有用处：看清楚全世界正在试哪些药、做到了哪一期、由谁在做。把药名和 NCT 编号记下来去问主治医生，或据此进一步查该药是否已在境外获批、是否有拓展性用药（expanded access）通道。

美国9法国3加拿大2西班牙1意大利1澳大利亚1以色列1

共 19 项。

  • 招募中NCT07434037
    The Neurocognitive Bases of Trust in Intellectual Disability
    观察性 · 2026/07/17Hospices Civils de Lyon
    法国
  • 招募中NCT07654114
    Safety, Tolerability, and Preliminary Effectiveness of CTH120 in Fragile X Syndrome
    II 期 · 干预性 · 2026/05/21Connecta Therapeutics, S.L.
    西班牙
  • 招募中NCT06868979
    Optical Imaging in X-linked Disorders.
    不适用 · 干预性 · 2026/03/30Hospices Civils de Lyon
    法国
  • 招募中NCT07493096
    Intensive Multimodal Neurorehabilitation Targeting Neuroplasticity in Pediatric Neurodevelopmental and Chromosomal Disorders
    观察性 · 2026/03/01Healing Hope International
    美国
  • 尚未开始招募NCT07439510
    A Study to Investigate the Effects and Safety of SPG601 for the Treatment of Fragile X Syndrome in Male Participants
    II 期、III 期 · 干预性 · 2026/03/01Spinogenix
  • 尚未开始招募NCT07328529
    Inhibition of Aggressive Behavior in Participants With Fragile X Syndrome
    II 期 · 干预性 · 2026/03Azevan Pharmaceuticals
    美国
  • 招募中NCT07209462
    Study of MRM-3379 in Male Participants With Fragile X Syndrome (BLOOM)
    II 期 · 干预性 · 2025/11/22Mirum Pharmaceuticals, Inc.
    美国
  • 招募中NCT06261502
    Effect of CANnabidiol on Anxiety and GABAergic Function in Individuals With Fragile-X Syndrome
    II 期 · 干预性 · 2025/09/01Université de Sherbrooke
    加拿大
  • 尚未开始招募NCT06261450
    Effect of CBD on the Brain
    II 期 · 干预性 · 2025/05/01Université de Sherbrooke
  • 招募中NCT06740162
    Physical Activity and Community EmPOWERment Project
    不适用 · 干预性 · 2025/01/10University of North Carolina, Chapel Hill
    美国
  • 招募中NCT06147414
    Development of Non-Invasive Prenatal Diagnosis for Single Gene Disorders
    观察性 · 2024/10/23Assistance Publique - Hôpitaux de Paris
    法国
  • 招募中NCT06081348
    Sertraline vs. Placebo in the Treatment of Anxiety in Children and AdoLescents With NeurodevelopMental Disorders
    II 期 · 干预性 · 2024/09/16Holland Bloorview Kids Rehabilitation Hospital
    加拿大
  • 招募中NCT06088589
    Speech-in-noise Perception in Autism and Fragile X
    不适用 · 干预性 · 2023/11/10Children's Hospital Medical Center, Cincinnati
    美国
  • 招募中NCT06227780
    Alpha Auditory Entrainment for Cognitive Enhancement and Sensory Hypersensitivity in Youth With Developmental Disorders
    不适用 · 干预性 · 2023/05/24Children's Hospital Medical Center, Cincinnati
    美国
  • 招募中NCT06560242
    Tracking Early Emergence of Sound Perception Impairments in FXS With Multimodal fNIRS/EEG- Infant
    不适用 · 干预性 · 2022/10/31Children's Hospital Medical Center, Cincinnati
    美国

外部标识与链接

OrphanetOMIM:300624OMIM:311360MONDO:0010383GARD:6464ICD-10 Q99.2ICD-11 LD55ClinicalTrials.gov 检索

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本页数据来源

  • 疾病定义、同义词、基因、表型、流行病学：Orphanet（CC BY 4.0）
  • 中文病名：Orphanet 中文包，冻结于 2020-06-01
  • 表型中文标签：HPO 简体中文翻译（CHPO 上游成果）