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Angelman syndrome

ORPHA:72疾病中国目录 第1批 · 5

定义 英文原文（暂无中文）

A rare genetic neurodevelopmental disorder characterized by moderate to severe intellectual disability, microcephaly, seizures, ataxic gait and distinct abnormal facial shape.

基本事实

遗传方式
不适用
发病年龄
婴儿期
患病率
1-9 / 100 000

相关基因 1来自下位疾病

Orphanet 未在本条目上直接标注致病基因。下表由本组所属的下位疾病汇总而来，「来源条目」列给出基因实际标注在哪一个 ORPHA 条目上。

基因名称来源条目
UBE3Aubiquitin protein ligase E3AORPHA:411511

临床表型 71

极常见 99–80%19

  • 异常言语模式 HP:0002167
  • 共济失调 HP:0001251
  • 非典型行为 HP:0000708
  • 自闭症行为 HP:0000729
  • 宽基步态 HP:0002136
  • 大脑皮层萎缩 HP:0002120
  • 语言发育迟缓 HP:0000750
  • 脑电图异常 HP:0002353
  • 多动症 HP:0000752
  • 不适宜的发笑 HP:0000748
  • 重度智力障碍 HP:0010864
  • 小头畸形 HP:0000252
  • 运动发育迟缓 HP:0001270
  • 少言寡语 HP:0002465
  • 癫痫发作 HP:0001250
  • 自伤行为 HP:0100716
  • 严重的全面性发育迟缓 HP:0011344
  • 睡眠异常 HP:0002360
  • 震颤 HP:0001337

常见 79–30%19

  • 面部形状异常 HP:0001999
  • 胃肠道异常 HP:0011024
  • 散光 HP:0000483
  • 便秘 HP:0002019
  • 流涎 HP:0002307
  • 金发 HP:0002286
  • 喂养困难 HP:0011968
  • 婴儿型肌张力减退 HP:0008947
  • 胃食管反流 HP:0002020
  • 皮肤色素减退 HP:0001010
  • 虹膜色素减退 HP:0007730
  • 肥胖 HP:0001513
  • 多食 HP:0002591
  • 舌头过长 HP:0010808
  • 反复用手拍打 HP:0100023
  • 脊柱侧弯 HP:0002650
  • 睡眠-觉醒周期紊乱 HP:0006979
  • 斜视 HP:0000486
  • 宽嘴 HP:0000154

偶见 29–5%32

  • 语言缺失 HP:0001344
  • 攻击性行为 HP:0000718
  • 弱视 HP:0000646
  • 焦虑 HP:0000739
  • 失张力癫痫发作 HP:0010819
  • 非典型失神发作 HP:0007270
  • 脑髓鞘形成障碍 HP:0007266
  • 月经初潮延迟 HP:0012569
  • 吞咽困难 HP:0002015
  • 枕骨扁平 HP:0005469
  • 婴儿期胃造口管饲 HP:0011471
  • 全面性肌阵挛发作 HP:0002123
  • 快乐举止 HP:0040082
  • 远视 HP:0000540
  • 行走不能 HP:0002540
  • 圆锥角膜 HP:0000563
  • 下颌前突 HP:0000303
  • 肌阵挛 HP:0001336
  • 近视 HP:0000545
  • 鼻胃管灌食 HP:0040288
  • 眼球震颤 HP:0000639
  • 视神经萎缩 HP:0000648
  • 视盘苍白 HP:0000543
  • 足外翻 HP:0008081
  • 吸吮无力 HP:0002033
  • 女性性早熟 HP:0010465
  • 上睑下垂 HP:0000508
  • 减少目光接触 HP:0000817
  • 癫痫持续状态 HP:0002133
  • 吐舌习惯 HP:0100703
  • 呕吐 HP:0002013
  • 牙间隙增宽 HP:0000687

罕见 <4–1%1

  • 婴儿痉挛 HP:0012469

近两年的全球研究 982L2

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。

  • 2026-09开放获取
    Genetic Etiologies of Dystonia with Anarthria/Aphonia
    Movement disorders clinical practice · DOI · Europe PMC
  • 2026-09
    Establishing meaningful score differences for the observer-reported communication ability (ORCA) measure using the scale judgment approach with caregivers of individuals with Angelman syndrome
    Quality of life research : an international journal of quality of life · DOI · Europe PMC
  • 2026-09综述
    Targeted Epigenetic Reactivation strategies as new treatments for Prader-Willi Syndrome: Achievements and Challenges
    Molecular therapy : the journal of the American Society of Gene Therap · DOI · Europe PMC
  • 2026-09开放获取
    Clinical and genetic spectrum of dual rare genetic diseases revealed by whole-exome sequencing in 14 pediatric patients
    Orphanet journal of rare diseases · DOI · Europe PMC
  • 2026-09综述开放获取
    Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-09综述开放获取
    E3 Ubiquitin Ligases in Neurodevelopmental Disorders
    Cells · DOI · Europe PMC
  • 2026-09病例报告
    First Report of Uniparental Isodisomy of Chromosome 15 Revealing Angelman Syndrome and Microphthalmia Associated With a Novel Homozygous ALDH1A3 Variant
    American journal of medical genetics. Part A · DOI · Europe PMC
  • 2026-09综述开放获取
    The Lactate-Lactylation Axis as a Metabolic-Epigenetic Framework for Therapeutic Adaptation in Esophageal Squamous Cell Carcinoma
    Cancers · DOI · Europe PMC
  • 2026-09综述开放获取
    &lt;i&gt;Drosophila melanogaster&lt;/i&gt; as a Model for Autism Spectrum Disorder: Insights into Lifelong Neuronal Vulnerability
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-09综述开放获取
    3D Genome Engineering Using CRISPR/dCas Systems
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-09综述
    Novel and Emerging Therapies for Childhood-Onset Movement Disorders
    Movement disorders : official journal of the Movement Disorder Society · DOI · Europe PMC
  • 2026-09开放获取
    Author response to Commentary on "Long-term safety and efficacy of deoxycytidine/deoxythymidine in treatment of POLG-related disorders"
    Neurotherapeutics : the journal of the American Society for Experiment · DOI · Europe PMC
  • 2026-09
    Treatment responses to antiseizure medication in children with Angelman syndrome
    European journal of paediatric neurology : EJPN : official journal of · DOI · Europe PMC
  • 2026-09开放获取
    Identification of the Genomic Etiology of Unexplained Congenital Problems in Pediatric Patients: First Reported Case With Coffin-Siris Syndrome and Sialuria From India
    Clinical case reports · DOI · Europe PMC
  • 2026-09
    Understanding positive affect in Angelman syndrome: Smiling and laughter across comparison groups
    Research in developmental disabilities · DOI · Europe PMC
  • 2026-09开放获取
    Cell-type-specific dysregulated gene expression in the frontal cortex of an Angelman syndrome pig model
    Human molecular genetics · DOI · Europe PMC
  • 2026-09综述
    Written in the Stars: Astrocyte Biology From Evolution to Disease
    Acta physiologica (Oxford, England) · DOI · Europe PMC
  • 2026-09综述开放获取
    Epigenetic, environmental, and sex-specific programming of long-term health in Assisted Reproductive Technologies-conceived offspring†
    Biology of reproduction · DOI · Europe PMC
  • 2026-09开放获取
    Performance and Biases of the LENA and ACLEW Algorithms in Analyzing Language Environments in Down, Fragile X, Angelman Syndromes, and Populations at Elevated Likelihood for Autism
    Developmental science · DOI · Europe PMC
  • 2026-08综述开放获取
    Diagnostic Yield and Clinical Utility of Chromosomal Microarray Analysis (CMA) in Children With Developmental Delay, Intellectual Disability, and Autism Spectrum Disorder: A Systematic Review
    Cureus · 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（19 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。

  • recombinant adeno-associated viral vector serotype 9 carrying the gene欧盟2016-04-28
    Treatment of Angelman syndrome
    官方记录
  • Gaboxadol monohydrate欧盟2019-06-28
    Treatment of Angelman syndrome
    官方记录
  • synthetic oligonucleotide selectively targeting UBE3A antisense RNA tr欧盟2020-12-09
    Treatment of Angelman syndrome
    官方记录
  • Cyclo-L-glycyl-L-2-allylproline欧盟2021-01-06
    Treatment of Angelman syndrome
    官方记录
  • adeno-associated virus serotype PTC3 expressing the human UBE3A gene欧盟2021-08-20
    Treatment of Angelman syndrome
    官方记录
  • 2'-O-(2-methoxyethyl) modified antisense oligonucleotide targeting UBE欧盟2022-06-21
    Treatment of Angelman syndrome
    官方记录
  • 2'-O, 4'-C-Methylene-P-thio-adenylyl-(3'->5')-2'-O, 4'-C-methylene-P-t欧盟2023-12-13
    Treatment of Angelman syndrome
    官方记录
  • recombinant adeno-associated virus serotype 9 vector containing the tr美国2015-10-29
    Treatment of Angelman Syndrome.
    官方记录
  • 4,5,6,7-tetrahydroisoxazolo(5,4-c)pyridin-3-ol美国2016-09-06
    Treatment of Angelman syndrome.
    官方记录
  • [(4-benzylpiperazin-1-yl)(2-(isopentylamino)pyridin-3-yl)methanone]-ph美国2018-08-07
    Treatment of Angelman Syndrome
    官方记录
  • Chimeric locked nucleic acid and ribonucleic-deoxyribonucleic antisens美国2019-08-28
    Treatment of Angelman syndrome
    官方记录
  • cyclo(-L-Glycyl-L-2-Allylproline)美国2019-10-09
    Treatment of Angelman syndrome
    官方记录
  • Recombinant adeno-associated virus vector containing the active biolog美国2020-10-22
    Treatment of Angelman Syndrome
    官方记录
  • UBE3A antisense oligonucleotide with locked nucleic acids (UBE3A-ATS-L美国2020-11-24
    Treatment of Angelman Syndrome
    官方记录
  • Cannabidiol美国2021-03-22
    Treatment of Angelman syndrome
    官方记录
  • 2'-O-(2-methoxyethyl) modified antisense oligonucleotide targeting UBE美国2022-05-26
    Treatment of Angelman Syndrome
    官方记录
  • 14-species commensal bacterial flora with prebiotics and postbiotic co美国2024-04-29
    treatment of Angelman syndrome
    官方记录
  • insulin like growth factor 2 receptor ligand美国2024-07-03
    treatment of Angelman syndrome.
    官方记录
  • non-replicating recombinant adeno-associated virus serotype hu68 (AAVh美国2025-10-16
    treatment of Angelman syndrome
    官方记录

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NCT03358823
    Study on the Brain Network of Angelman Syndrome
    观察性 · 2017/05/20Fudan University
    中国研究中心 1 个：Shanghai

中国境外的在招试验 12L2

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5澳大利亚2加拿大2意大利2法国2德国1以色列1日本1波兰1新加坡1韩国1西班牙1英国1比利时1

共 12 项。

  • 尚未开始招募NCT07782827
    CHAMPION: A Study to Evaluate the Efficacy and Safety of Obudanersen (ION582) in Children and Adults With Angelman Syndrome (AS)
    III 期 · 干预性 · 2026/09Ionis Pharmaceuticals, Inc.
  • 招募中NCT07417137
    A Natural History Study of Angelman Syndrome
    观察性 · 2026/08Massachusetts General Hospital
    美国
  • 招募中NCT07605429
    BEACON - Phase III Clinical Study of Rugonersen in Angelman Syndrome.
    III 期 · 干预性 · 2026/06/23OHB Pediatrics Ltd.
    美国
  • 招募中NCT07181837
    A Phase 1/2 Study of the Safety and Efficacy of MVX-220 in Angelman Syndrome
    I 期、II 期 · 干预性 · 2025/10/29MavriX Bio, LLC
    美国
  • 招募中NCT06914609
    REVEAL: A Phase 3 Study of Obudanersen (ION582) in Angelman Syndrome
    III 期 · 干预性 · 2025/06/10Ionis Pharmaceuticals, Inc.
    澳大利亚、加拿大、德国、以色列、意大利、日本、波兰、新加坡 等 12 国
  • 招募中NCT06737718
    Use of Eye Tracking to Study Social Perception Abnormalities in Children With Angelman Syndrome
    观察性 · 2025/02/25Assistance Publique - Hôpitaux de Paris
    法国
  • 招募中NCT06353620
    Structural-functional Connectome in Drug-resistant Epilepsies and Neurodevelopmental Syndromes With Epilepsy
    观察性 · 2024/02/13IRCCS Eugenio Medea
    意大利
  • 招募中NCT06229769
    Natural History Study for Patients With Angelman Syndrome
    观察性 · 2021/10/10Centre Hospitalier Universitaire de Liege
    比利时
  • 招募中NCT04507997
    Angelman Syndrome Natural History Study
    观察性 · 2018/08/01Boston Children's Hospital
    加拿大、美国
  • 招募中NCT05945576
    IDMet (RaDiCo Cohort) (RaDiCo-IDMet)
    观察性 · 2017/03/10Institut National de la Santé Et de la Recherche Médicale, France
    法国
  • 招募中NCT05293184
    The Global Angelman Syndrome Registry
    观察性 · 2016/09/28Foundation for Angelman Syndrome Therapeutics, Australia
    澳大利亚
  • 可获取（拓展性用药）NCT07136454
    Expanded Access/Compassionate Use of Rugonersen in Patients With Angelman Syndrome
    拓展性用药Oak Hill Bio Ltd

外部标识与链接

OrphanetOMIM:105830MONDO:0007113GARD:5810ICD-10 Q93.5ICD-11 LD90.0ClinicalTrials.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）