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先天性肌无力综合征

Congenital myasthenic syndrome

ORPHA:590疾病中国目录 第1批 · 21

定义 英文原文（暂无中文）

A rare genetic neuromuscular disease characterized by impaired transmission at the neuromuscular junction, typically presenting in infancy or childhood, although later onset is possible. The hallmark symptom is muscle fatigability, frequently accompanied by ocular manifestations (ptosis, ophthalmoparesis), bulbar involvement (dysphagia), a generalized weakness, which can lead to potentially life-threatening respiratory insufficiency.

别名

CMS

基本事实

遗传方式
常染色体显性、常染色体隐性
发病年龄
婴儿期、新生儿期
患病率
1-9 / 1 000 000（Europe）

临床表型 68

极常见 99–80%10

  • 吞咽困难 HP:0002015
  • 疲劳性肌无力 HP:0003473
  • 喂养困难 HP:0011968
  • 额肌乏力 HP:0004661
  • 肌无力所致的间歇性呼吸功能不全发作 HP:0004889
  • 颈肌无力 HP:0000467
  • 吸吮无力 HP:0002033
  • 近端肌肉无力 HP:0003701
  • 上睑下垂 HP:0000508
  • 突然发作性呼吸暂停 HP:0002882

常见 79–30%20

  • 因疾病、疲劳、紧张而导致的呼吸暂停发作 HP:0002872
  • 先天性多发性关节挛缩 HP:0002804
  • 共济失调 HP:0001251
  • 球麻痹 HP:0001283
  • 中枢性睡眠呼吸暂停 HP:0010536
  • 窒息发作 HP:0030842
  • 紫绀 HP:0000961
  • 胎动减少 HP:0001558
  • 肌电图:神经肌肉接头传递受损 HP:0100285
  • 易疲劳性 HP:0003388
  • 阵发性呼吸窘迫 HP:0004885
  • 步态异常 HP:0001288
  • 泛发性肌无力 HP:0003324
  • 鼻音过重的言语 HP:0001611
  • 智力障碍 HP:0001249
  • 肌纤维萎缩 HP:0100295
  • 鼻腔返流 HP:0011469
  • 眼肌麻痹 HP:0000602
  • 反复呼吸道感染 HP:0002205
  • 神经性脊柱关节病 HP:0008443

偶见 29–5%20

  • 神经反射消失 HP:0001284
  • 远端肌肉萎缩 HP:0003693
  • 下肢远端肌无力 HP:0009053
  • 发音困难 HP:0001618
  • EMG:肌病样异常 HP:0003458
  • 高腭 HP:0000218
  • 肌张力减退 HP:0001252
  • 脊柱后侧凸 HP:0002751
  • 肢带肌无力 HP:0003325
  • 长脸 HP:0000276
  • 运动发育迟缓 HP:0001270
  • 窄下颌 HP:0012801
  • 高弓足 HP:0001761
  • 头部控制能力弱 HP:0002421
  • 癫痫发作 HP:0001250
  • 脊柱强直 HP:0003306
  • 喘鸣 HP:0010307
  • 脚尖步 HP:0030051
  • 蹒跚步态 HP:0002515
  • 哭声微弱 HP:0001612

罕见 <4–1%17

  • 先天性髋关节脱位 HP:0001374
  • 复视 HP:0000651
  • 脑电图，伴多棘慢复合波 HP:0002392
  • 内斜视 HP:0000565
  • 胃食管反流 HP:0002020
  • 腱反射减弱 HP:0001265
  • 关节过度活动 HP:0001382
  • 低位耳 HP:0000369
  • 下颌小且后移 HP:0000308
  • 多发性运动神经病 HP:0007178
  • 眼球震颤 HP:0000639
  • 阻塞性睡眠呼吸暂停 HP:0002870
  • 鸡胸 HP:0000768
  • 羊水过多 HP:0001561
  • 呼吸骤停 HP:0005943
  • 感音神经性听力受损 HP:0000407
  • 凝视 HP:0025401

排除 0%1

  • 抗神经肌肉接头乙酰胆碱受体抗体阳性 HP:0030208

近两年的全球研究 238L2

2024/08 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。

  • 2026-07
    Congenital myasthenic syndromes in a Southeast Asian adult neurology clinic: a long road to diagnosis and therapy
    BMC neurology · DOI · Europe PMC
  • 2026-07
    Longitudinal behavioral profiling reveals early-onset and persistent motor dysfunction in a VAChT-KD model for congenital myasthenic syndrome
    Behavioural brain research · DOI · Europe PMC
  • 2026-07病例报告
    Benefit of Salbutamol for the Treatment of Neuromuscular Junction Dysfunction in Patients With Purine-Rich Element Binding Protein A (PURA) Syndrome
    Cureus · DOI · Europe PMC
  • 2026-07
    ALG14 variants contribute to a congenital disorder of glycosylation characterized by congenital myasthenia and epilepsy
    HGG advances · DOI · Europe PMC
  • 2026-07
    Genotypic and phenotypic spectrum of congenital myasthenic syndrome: Insights from Southeastern Türkiye
    European journal of paediatric neurology : EJPN : official journal of · DOI · Europe PMC
  • 2026-07综述
    Review of Congenital Myasthenic Syndrome Caused by Pathogenic Variants in GFPT1
    Muscle & nerve · DOI · Europe PMC
  • 2026-07综述
    AGRN-, LRP4-, MUSK-Related CMS: Clinical, Neurophysiological, Morphological, Genetic and Pathological Mechanisms
    Muscle & nerve · DOI · Europe PMC
  • 2026-07综述
    The Differing Phenotypes of the Three Most Common Postsynaptic Congenital Myasthenic Syndromes Governed by Their Underlying Molecular Pathogenic Mechanisms
    Muscle & nerve · DOI · Europe PMC
  • 2026-07病例报告
    Distal Agrin (AGRN) Congenital Myasthenic Syndrome With Mitochondrial Dysfunction
    European journal of neurology · DOI · Europe PMC
  • 2026-06
    Hexosamine Pathway Disruption by GFPT1 Loss Drives Coordinated Defects in Glycosylation, Autophagy, and Trafficking
    Biomolecules · DOI · Europe PMC
  • 2026-06综述
    &lt;i&gt;LRP4&lt;/i&gt;-Related Congenital Myasthenic Syndrome: Clinical, Pathophysiological, and Therapeutic Aspects
    Muscles (Basel, Switzerland) · DOI · Europe PMC
  • 2026-06病例报告
    Postsynaptic Congenital Myasthenic Syndrome Mimicking Limb-Girdle Muscular Dystrophy Associated with an Alternatively Spliced Exon in CHRNB1: A Case Report and Literature Review
    Children (Basel, Switzerland) · DOI · Europe PMC
  • 2026-06病例报告
    Suspected Adult-Onset Congenital Myasthenic Syndrome Associated With a Heterozygous CHRND Variant in a Patient With Seropositive Rheumatoid Arthritis: A Case Report
    The American journal of case reports · DOI · Europe PMC
  • 2026-06开放获取
    Co-Occurrence of &lt;i&gt;SCN9A&lt;/i&gt; and &lt;i&gt;PRRT2&lt;/i&gt; Variants in a Patient With Paroxysmal Extreme Pain Disorder, Contradictory Analgesia, and Intractable Paroxysmal Non-Kinesigenic Dyskinesia
    Case reports in medicine · DOI · Europe PMC
  • 2026-06
    Familial dystroglycanopathy: same mutation, different phenotypes
    Practical neurology · DOI · Europe PMC
  • 2026-06
    Congenital myasthenic syndrome due to novel &lt;i&gt;GFPT1&lt;/i&gt; variant presenting with head drop and visual impairment: A case report
    Journal of neuromuscular diseases · DOI · Europe PMC
  • 2026-06
    Late diagnosis of RAPSN mutation-associated congenital myasthenic syndrome with obstructive sleep apnea in a 5-year-old girl
    BMC pediatrics · DOI · Europe PMC
  • 2026-06开放获取
    Positive allosteric modulator selective for adult muscle nicotinic acetylcholine receptor
    Proceedings of the National Academy of Sciences of the United States o · DOI · Europe PMC
  • 2026-06病例报告开放获取
    Postsynaptic Congenital Myasthenic Syndrome Mimicking Limb–Girdle Muscular Dystrophy Associated with an Alternatively Spliced Exon in CHRNB1: A Case Report and Literature Review
    Children (Basel, Switzerland)
  • 2026-06综述开放获取
    Arthrogryposis Multiplex Congenita: Comprehensive Review from a Neuromuscular Standpoint
    Genes

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。

已获孤儿药资格、尚未获批的在研药物（4 项）

孤儿药资格只是一种监管身份——它意味着监管机构认可这是罕见病用药并给予研发激励，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。

  • 3,4-diaminopyridine美国2017-03-30
    Treatment of congenital myasthenic syndrome (CMS)
    官方记录
  • AAV9 gene therapy encoding the Dok7 protein美国2020-11-19
    Treatment of congenital myasthenic syndrome
    官方记录
  • a fully humanized immunoglobulin gamma 1 (IgG1) agonistic monoclonal a美国2023-06-21
    Treatment of congenital myasthenic syndrome
    官方记录
  • adeno-associated virus serotype 9 human choline acetyltransferase (AVC美国2024-10-22
    treatment of congenital myasthenic syndrome
    官方记录

数据来自欧洲药品管理局（EMA）的药品与孤儿药资格公开导出表，以及美国 FDA 孤儿药资格数据库。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。

中国境外的在招试验 8L2

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6比利时2Antigua and Barbuda1奥地利1巴西1加拿大1法国1德国1意大利1日本1波兰1西班牙1英国1澳大利亚1

共 8 项。

  • 尚未开始招募NCT07746089
    A Study to Assess Efficacy and Safety of Adimanebart in Adult and Pediatric Participants With DOK7-,MUSK-, AGRN-, or LRP4- Congenital Myasthenic Syndromes (CMS)
    III 期 · 干预性 · 2026/09argenx
  • 招募中NCT07478172
    Effects of Whole-body Electrical Muscle Stimulation Exercise on Adults With Neuromuscular Disease
    不适用 · 干预性 · 2026/03/10University of Missouri-Columbia
    美国
  • 招募中NCT06630650
    A Prospective Natural History and Outcome Measure Validation Study of Congenital Myasthenic Syndromes
    观察性 · 2025/05/12National Institute of Neurological Disorders and Stroke (NINDS)
    美国
  • 招募中NCT07226726
    Patients With Congenital Myasthenic Syndrome Will be Treated With Mesenchymal Stem Cell Exosome Solution
    I 期 · 干预性 · 2025/01/01The Foundation for Orthopaedics and Regenerative Medicine
    Antigua and Barbuda、美国
  • 招募中NCT07136844
    Gait Analysis Parameter and Upper Limb Evaluation in Adult Patients With Neurological or Metabolic Pathology
    不适用 · 干预性 · 2024/03/29Centre Hospitalier Universitaire de Liege
    比利时
  • 招募中NCT06078553
    A Natural History Study in Participants With Congenital Myasthenic Syndromes (CMS) Due to Mutations in DOK7, MUSK, AGRN, or LRP4
    观察性 · 2024/02/13argenx
    奥地利、比利时、巴西、加拿大、法国、德国、意大利、日本 等 12 国
  • 招募中NCT01793168
    Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford
    观察性 · 2010/07Sanford Health
    澳大利亚、美国
  • 招募中NCT01403402
    Congenital Muscle Disease Study of Patient and Family Reported Medical Information
    观察性 · 2009/09Cure CMD
    美国

外部标识与链接

OrphanetOMIM:254190OMIM:254210OMIM:254300MONDO:0018940GARD:11902ICD-10 G70.2ICD-11 8C61ClinicalTrials.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）