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Noonan综合征

Noonan syndrome

ORPHA:648疾病中国目录 第1批 · 84

定义 英文原文（暂无中文）

A rare, highly variable, multisystemic disorder mainly characterized by short stature, distinctive facial features, congenital heart defects, cardiomyopathy and an increased risk to develop tumors in childhood.

基本事实

遗传方式
常染色体显性、常染色体隐性
发病年龄
产前、儿童期、婴儿期、新生儿期
患病率
6-9 / 10 000（United States）

相关基因 15

基因名称关联类型
PTPN11protein tyrosine phosphatase non-receptor type 11Disease-causing germline mutation(s) in
BRAFB-Raf proto-oncogene, serine/threonine kinaseDisease-causing germline mutation(s) in
SOS1SOS Ras/Rac guanine nucleotide exchange factor 1Disease-causing germline mutation(s) (gain of function) in
KRASKRAS proto-oncogene, GTPaseDisease-causing germline mutation(s) in
RAF1Raf-1 proto-oncogene, serine/threonine kinaseDisease-causing germline mutation(s) (gain of function) in
NRASNRAS proto-oncogene, GTPaseDisease-causing germline mutation(s) in
CBLCbl proto-oncogeneDisease-causing germline mutation(s) in
RIT1Ras like without CAAX 1Disease-causing germline mutation(s) (gain of function) in
LZTR1leucine zipper like post translational regulator 1Disease-causing germline mutation(s) in
RASA2RAS p21 protein activator 2Disease-causing germline mutation(s) (loss of function) in
SOS2SOS Ras/Rho guanine nucleotide exchange factor 2Disease-causing germline mutation(s) in
RRASRAS relatedCandidate gene tested in
MRASmuscle RAS oncogene homologDisease-causing germline mutation(s) in
RRAS2RAS related 2Disease-causing germline mutation(s) in
SPRED2sprouty related EVH1 domain containing 2Disease-causing germline mutation(s) in

临床表型 70

极常见 99–80%29

  • 异常心电图 HP:0003115
  • 心血管系统形态异常 HP:0030680
  • 异常言语模式 HP:0002167
  • 腹壁肌群发育不良/发育不全 HP:0010318
  • 囊状水瘤 HP:0000476
  • 下斜睑裂 HP:0000494
  • 构音障碍 HP:0001260
  • 胸廓扩张 HP:0100625
  • 额头高 HP:0000348
  • 高腭 HP:0000218
  • 眼距过宽 HP:0000316
  • 低促性腺激素性性腺功能减退症 HP:0000044
  • 关节过度活动 HP:0001382
  • 小下颌 HP:0000347
  • 面中部后缩 HP:0011800
  • 肌无力 HP:0001324
  • 鸡胸 HP:0000768
  • 漏斗胸 HP:0000767
  • 后旋耳 HP:0000358
  • 眼球突出 HP:0000520
  • 上睑下垂 HP:0000508
  • 肺动脉狭窄 HP:0004415
  • 身材矮小 HP:0004322
  • 厚下红唇 HP:0000179
  • 耳轮增厚 HP:0000391
  • 颈部皮肤皱襞增厚 HP:0000474
  • 三角脸 HP:0000325
  • 蹼颈 HP:0000465
  • 乳头间距宽 HP:0006610

常见 79–30%21

  • 异常出血 HP:0001892
  • 皮纹异常 HP:0007477
  • 毛发数量异常 HP:0011362
  • 血小板功能异常 HP:0011869
  • 肺动脉瓣形态异常 HP:0001641
  • 凝血异常 HP:0001928
  • 生殖系统异常 HP:0000078
  • 淋巴系统异常 HP:0100763
  • 脾脏异常 HP:0001743
  • 心律失常 HP:0011675
  • 蓝色虹膜 HP:0000635
  • 毛发粗糙 HP:0002208
  • 隐睾 HP:0000028
  • 骨成熟延迟 HP:0002750
  • 婴儿期喂养困难 HP:0008872
  • 肝脏肿大 HP:0002240
  • 肌张力减退 HP:0001252
  • 后发际低 HP:0002162
  • 神经发育延迟 HP:0012758
  • 脊柱侧弯 HP:0002650
  • 斜视 HP:0000486

偶见 29–5%19

  • 半规管不发育 HP:0011381
  • 房间隔缺损 HP:0001631
  • 短指（趾） HP:0001156
  • 瘀斑易感性 HP:0000978
  • 第五指屈指畸形 HP:0004209
  • 主动脉缩窄 HP:0001680
  • 月经初潮延迟 HP:0012569
  • 肾盂扩张 HP:0010946
  • 肥厚型心肌病 HP:0001639
  • 智力障碍 HP:0001249
  • 青少年型粒单核细胞白血病 HP:0012209
  • 淋巴水肿 HP:0001004
  • 黑素细胞痣 HP:0000995
  • 眼球震颤 HP:0000639
  • 骨质减少 HP:0000938
  • 出生后生长迟缓 HP:0008897
  • 桡尺骨融合 HP:0002974
  • 感音神经性听力受损 HP:0000407
  • 特定的学习障碍 HP:0001328

罕见 <4–1%1

  • 动脉导管未闭 HP:0001643

近两年的全球研究 1,222L2

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。

  • 2026-08
    Clinical and Genetic Profile of One Molecularly Confirmed and One Clinically Suspected Case of LZTR1-Related Noonan Syndrome
    Clinical genetics · DOI · Europe PMC
  • 2026-07
    Real-World Effectiveness and Safety of Recombinant Human Growth Hormone in Chinese Children with Noonan Syndrome: Long-Term Follow-up and a 2-Year Comparison of Short- and Long-Acting Formulations
    Hormone and metabolic research = Hormon- und Stoffwechselforschung = H · DOI · Europe PMC
  • 2026-07病例报告
    MEK Inhibitor Associated Airway Injury in an Infant With Noonan Syndrome: A Case Report
    The Laryngoscope · DOI · Europe PMC
  • 2026-07
    Hepatoblastoma in an Infant With Germline PTPN11 Variant and Noonan Syndrome: A Case Report
    Pediatric blood & cancer · DOI · Europe PMC
  • 2026-07
    Foveal Hypoplasia in a Patient with Noonan Syndrome
    Ophthalmology. Retina · DOI · Europe PMC
  • 2026-07
    Well-Differentiated Papillary Mesothelioma in a Child With SOS1-Related Noonan Syndrome
    Pediatric blood & cancer · DOI · Europe PMC
  • 2026-07
    Clinical and Molecular Characterization of a RASopathy Cohort From Türkiye and an AMMECR1-Related Noonan Syndrome-Mimicking Phenotype
    Clinical genetics · DOI · Europe PMC
  • 2026-07
    Impact of RASopathy subtype on the early disease course of RASopathy-associated hypertrophic cardiomyopathy: clinical outcomes and genetic insights
    Pediatric research · DOI · Europe PMC
  • 2026-07
    22q11.2 duplication syndrome and LZTR1-related Noonan syndrome type 10 overlapping phenotypes in a dual diagnosis - fetal hydrops: a case report
    BMC pregnancy and childbirth · DOI · Europe PMC
  • 2026-07
    Genetic Spectrum of Non-PTPN11 Variants in Noonan Syndrome and Related RASopathies: Findings From a Russian Cohort
    Clinical genetics · DOI · Europe PMC
  • 2026-07病例报告
    Coronary Artery Aneurysms and Dilation in Children With RASopathies
    JACC. Case reports · DOI · Europe PMC
  • 2026-07病例报告
    A case of cystic hygroma with confined placental mosaicism of tetraploidy leading to noonan syndrome
    Taiwanese journal of obstetrics & gynecology · DOI · Europe PMC
  • 2026-07开放获取
    Disrupted Vestibular Nuclei Neuron Development in a Chick Model for Congenital Vestibular Disorders
    Developmental neurobiology · DOI · Europe PMC
  • 2026-07
    Characterization of Genetic Etiologic Factors for Pediatric Acute Lymphoblastic Leukemia in Large Childhood Cancer Survivorship Cohorts
    Cancer epidemiology, biomarkers & prevention : a publication of the Am · DOI · Europe PMC
  • 2026-06病例报告
    Intramural Duodenal Hematoma-A Rare Post-Endoscopy Complication in Pediatric Noonan Syndrome: A Case Report
    Pediatric reports · DOI · Europe PMC
  • 2026-06病例报告
    Endocardial radiofrequency ablation for the treatment of pediatric hypertrophic cardiomyopathy: A report of two cases and a brief review of the literature
    Medicine international · DOI · Europe PMC
  • 2026-06
    An Unexpected Result in a Case of Gonadal Dysgenesis: Noonan Syndrome Caused by &lt;i&gt;RIT1&lt;/i&gt; Mutation
    Journal of clinical research in pediatric endocrinology · DOI · Europe PMC
  • 2026-06病例报告
    Multidisciplinary Dental Rehabilitation in an Adult with Noonan Syndrome: A Case Report
    Cureus · DOI · Europe PMC
  • 2026-06
    LMS Parameter Errors in Noonan Syndrome Growth Charts
    Hormone research in paediatrics · DOI · Europe PMC
  • 2026-06
    Early neonatal death due to prenatally undiagnosed congenital subglottic stenosis in Noonan syndrome
    BMC pregnancy and childbirth · DOI · Europe PMC

境外已获批用于本病的药物 1L2

欧盟 0 项、美国 1 项。同一药物在两地各批一次的，会分别列出。

「境外已获批」不等于「在中国能用」。中间隔着进口注册、临床急需境外新药通道、海南博鳌乐城国际医疗旅游先行区等几条路径，各有各的条件与费用。这一节能确定地告诉你的只有一件事：这个病在世界范围内已经有获得批准的药物，它叫什么名字。拿这个名字去问主治医生，是下一步最省力的做法。

药名一律保留英文原文，不作翻译——中国的药品通用名与英文名的音译经常不一致，译错会让人去找一个不存在的药。

已获孤儿药资格、尚未获批的在研药物（2 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。

  • Dasatinib美国2020-10-26
    Treatment of Noonan syndrome-associated hypertrophic cardiomyopathy
    官方记录
  • vosoritide美国2024-10-11
    treatment of short stature in Noonan 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。

在中国开展的临床试验 4L2

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。

登记为可入组 1

  • 招募中NCT07336394
    Precision Diagnosis and Risk Stratification of Rare Cardiomyopathies Based on Novel Cardiac Magnetic Resonance Techniques
    观察性 · 2010/01/01Chinese Academy of Medical Sciences, Fuwai Hospital
    中国研究中心 1 个：Beijing
其他状态的试验（3 项）
  • 已完成NCT03565003
    A First-in-Human Study of JAB-3068 (SHP2 Inhibitor) in Adult Patients With Advanced Solid Tumors in China
    I 期、II 期 · 干预性 · 2018/11/20Jacobio Pharmaceuticals Co., Ltd.
    中国研究中心 4 个：Beijing
  • 已完成NCT04121286
    A Study of JAB-3312 in Adult Patients With Advanced Solid Tumors in China
    I 期 · 干预性 · 2020/07/14Allist Pharmaceuticals, Inc.
    中国研究中心 5 个：Beijing、Henan
  • 进行中·不再招募NCT05330325
    A Research Study to Compare Somapacitan Once a Week With Norditropin® Once a Day in Children Who Need Help to Grow
    III 期 · 干预性 · 2022/08/10Novo Nordisk A/S
    中国研究中心 14 个：Beijing、Changchun、Changsha、Chengdu、Guangzhou、Jinan 等 11 地

中国境外的在招试验 15L2

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7法国5意大利4德国2西班牙2罗马尼亚1韩国1澳大利亚1加拿大1波兰1荷兰1

CT.gov 报告命中 15 项，此处取回并展示最近的 14 项。

  • 招募中NCT07493239
    A Decentralized Clinical Study Evaluating the Effectiveness of Two Different Doses of MyCondro™ on Physical Mobility and Joint Health
    不适用 · 干预性 · 2026/03/04Lesaffre International
    美国
  • 尚未开始招募NCT07259135
    Link Between Abnormal Bleeding and Coagulation Disorders in Noonan Syndromes
    观察性 · 2026/01University Hospital, Bordeaux
    法国
  • 招募中NCT07221851
    Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
    III 期 · 干预性 · 2025/12/12Ascendis Pharma A/S
    法国、德国、意大利、罗马尼亚、韩国、西班牙、美国
  • 招募中NCT07464821
    National Multicentre Study on Lipid Profile in Noonan Syndrome and Related Disorders: Trends by Age, Gender and Genotype
    观察性 · 2025/02/26IRCCS Azienda Ospedaliero-Universitaria di Bologna
    意大利
  • 招募中NCT06668805
    A Study of Vosoritide in Children With Noonan Syndrome With Inadequate Growth During or After Human Growth Hormone Treatment
    II 期 · 干预性 · 2024/11/22BioMarin Pharmaceutical
    澳大利亚、加拿大、法国、德国、意大利、西班牙、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NCT06555237
    MEK Inhibitors for the Treatment of Hypertrophic Cardiomyopathy in Patients With RASopathies
    II 期 · 干预性 · 2024/08/01Medical University of Warsaw
    波兰
  • 招募中NCT05361811
    Acceptance and Commitment Therapy for Caregivers of Children With a RASopathy: An Internal Pilot Feasibility Study and Follow-up Randomized Controlled Trial
    不适用 · 干预性 · 2024/01/10National Cancer Institute (NCI)
    美国
  • 招募中NCT04888936
    Clinical, Genetic, and Epidemiologic Study of Children and Adults With RASopathies
    观察性 · 2022/04/25National Cancer Institute (NCI)
    美国
  • 招募中NCT05202210
    Constitution of a Biological Collection to Study the Pathophysiology in Noonan Syndrome
    观察性 · 2022/01/26University Hospital, Toulouse
    法国
  • 招募中NCT05761314
    Solid Tumors in RASopathies
    不适用 · 干预性 · 2021/10/12Fondazione Policlinico Universitario Agostino Gemelli IRCCS
    意大利
  • 招募中NCT04463316
    GROWing Up With Rare GENEtic Syndromes
    观察性 · 2018/10/01dr. Laura C. G. de Graaff-Herder
    荷兰
  • 招募中NCT04395495
    RASopathy Biorepository
    观察性 · 2017/06/27Children's Hospital Medical Center, Cincinnati
    美国
  • 招募中NCT03050268
    Familial Investigations of Childhood Cancer Predisposition
    观察性 · 2017/04/06St. Jude Children's Research Hospital
    美国

外部标识与链接

OrphanetOMIM:163950OMIM:605275OMIM:609942MONDO:0018997GARD:10955ICD-10 Q87.1ICD-11 LD2F.15ClinicalTrials.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）