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Kallmann综合征

Kallmann syndrome

ORPHA:478疾病亚型中国目录 第1批 · 59

定义 英文原文（暂无中文）

Kallmann syndrome (KS) is a developmental genetic disorder characterized by the association of congenital hypogonadotropic hypogonadism (CHH) due to gonadotropin-releasing hormone (GnRH) deficiency, and anosmia or hyposmia (with hypoplasia or aplasia of the olfactory bulbs).

别名

先天性低促性腺激素性功能减退症伴嗅觉丧失

基本事实

遗传方式
常染色体显性、常染色体隐性、多基因/多因素、X 连锁隐性
发病年龄
青少年期、儿童期
患病率
1-9 / 100 000（Europe）

相关基因 23

基因名称关联类型
PROK2prokineticin 2Disease-causing germline mutation(s) (loss of function) in
PROKR2prokineticin receptor 2Disease-causing germline mutation(s) (loss of function) in
CHD7chromodomain helicase DNA binding protein 7Disease-causing germline mutation(s) in
SOX10SRY-box transcription factor 10Disease-causing germline mutation(s) (loss of function) in
FGFR1fibroblast growth factor receptor 1Disease-causing germline mutation(s) (loss of function) in
HESX1HESX homeobox 1Disease-causing germline mutation(s) in
ANOS1anosmin 1Disease-causing germline mutation(s) (loss of function) in
FGF8fibroblast growth factor 8Disease-causing germline mutation(s) (loss of function) in
TACR3tachykinin receptor 3Disease-causing germline mutation(s) in
WDR11WD repeat domain 11Disease-causing germline mutation(s) in
DCCDCC netrin 1 receptorDisease-causing germline mutation(s) (loss of function) in
HS6ST1heparan sulfate 6-O-sulfotransferase 1Disease-causing germline mutation(s) (loss of function) in
SEMA3Asemaphorin 3ADisease-causing germline mutation(s) (loss of function) in
IL17RDinterleukin 17 receptor DDisease-causing germline mutation(s) in
FGF17fibroblast growth factor 17Disease-causing germline mutation(s) in
DUSP6dual specificity phosphatase 6Disease-causing germline mutation(s) in
SPRY4sprouty RTK signaling antagonist 4Disease-causing germline mutation(s) in
FLRT3fibronectin leucine rich transmembrane protein 3Disease-causing germline mutation(s) in
FEZF1FEZ family zinc finger 1Disease-causing germline mutation(s) (loss of function) in
CCDC141coiled-coil domain containing 141Disease-causing germline mutation(s) in
CCDC141coiled-coil domain containing 141Major susceptibility factor in
NDNFneuron derived neurotrophic factorDisease-causing germline mutation(s) in
EMX2empty spiracles homeobox 2Disease-causing germline mutation(s) in

临床表型 44

极常见 99–80%11

  • 嗅觉缺失 HP:0000458
  • 垂体前叶功能减退症 HP:0000830
  • 生育能力下降 HP:0000144
  • 睾丸体积过小 HP:0008734
  • 青春期发育延迟 HP:0000823
  • 勃起功能障碍 HP:0100639
  • 低促性腺激素性性腺功能减退症 HP:0000044
  • 阴茎发育不良 HP:0008736
  • 嗅觉减退 HP:0004409
  • 下丘脑促性腺激素释放激素缺乏症 HP:0003164
  • 小阴茎 HP:0000054

常见 79–30%4

  • 声音异常 HP:0001608
  • 乳房发育不良 HP:0003187
  • 隐睾 HP:0000028
  • 骨密度降低 HP:0004349

偶见 29–5%29

  • 心血管系统形态异常 HP:0030680
  • 女性内生殖器形态异常 HP:0000008
  • 共济失调 HP:0001251
  • 双手联带运动 HP:0001335
  • 腭裂 HP:0000175
  • 色觉缺陷 HP:0000551
  • 骨成熟延迟 HP:0002750
  • 构音障碍 HP:0001260
  • 性交疼痛 HP:0030016
  • 步态异常 HP:0001288
  • 男子女性乳房发育 HP:0000771
  • 肌张力减退 HP:0001252
  • 鱼鳞病 HP:0008064
  • 肌无力 HP:0001324
  • 眼球震颤 HP:0000639
  • 肥胖 HP:0001513
  • 截瘫 HP:0010550
  • 高弓足 HP:0001761
  • 扁平足 HP:0001763
  • 原发性闭经 HP:0000786
  • 上睑下垂 HP:0000508
  • 复发性骨折 HP:0002757
  • 肾缺如 HP:0000104
  • 癫痫发作 HP:0001250
  • 感音神经性听力受损 HP:0000407
  • 骨骼发育不良 HP:0002652
  • 牙齿发育不全 HP:0009804
  • 震颤 HP:0001337
  • 视觉障碍 HP:0000505

近两年的全球研究 316L2

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
    Establishing the role of ZBTB20 mutations in GnRH deficiency and impaired neurogenesis in the subventricular zone: a human cohort and animal model study
    EBioMedicine · DOI · Europe PMC
  • 2026-08病例报告
    Double heterozygous PROK2 p.(Ile55Ter)-PROKR2 p.(Arg85Leu) variants: case report of an oligogenic case of congenital hypogonadotropic hypogonadism with anosmia
    Sexual development : genetics, molecular biology, evolution, endocrino · DOI · Europe PMC
  • 2026-07
    The Spectrum of Congenital Hypogonadotropic Hypogonadism: A 30-Year Experience at a Tertiary Paediatric Centre
    Clinical endocrinology · DOI · Europe PMC
  • 2026-07
    A Novel Hemizygous <i>ANOS1</i> Variant in a Patient With Kallmann Syndrome and Type 2 Diabetes Mellitus: A Case Report
    Case reports in endocrinology · DOI · Europe PMC
  • 2026-06综述
    Reversible congenital hypogonadotropic hypogonadism: keys for clinical management
    Archives of endocrinology and metabolism · DOI · Europe PMC
  • 2026-05开放获取
    Special Issue "Hormone Signaling in Human Health and Diseases"
    International journal of molecular sciences · DOI · Europe PMC
  • 2026-05开放获取
    Predictors of early response to GnRH and gonadotropin therapy in pediatric patients with suspected dual congenital hypogonadotropic hypogonadism: a retrospective single-center study
    Frontiers in endocrinology · DOI · Europe PMC
  • 2026-05综述
    Body composition in male hypogonadism: practical considerations to the use of dual-energy x-ray absorptiometry
    Reviews in endocrine & metabolic disorders · DOI · Europe PMC
  • 2026-05病例报告开放获取
    Fertility outcomes and management of long-term pubertal testosterone replacement sequelae in Oliver-McFarlane syndrome: a case report and literature review
    AME case reports · DOI · Europe PMC
  • 2026-05病例报告开放获取
    Successful Pregnancy in a Woman With Primary Infertility Associated With Isolated Hypogonadotropic Hypogonadism and Partial Empty Sella Syndrome: A Case Report
    Cureus · DOI · Europe PMC
  • 2026-05
    A de novo SOX11 mutation causing hypogonadotropic hypogonadism: a case report and literature review
    BMC pediatrics · DOI · Europe PMC
  • 2026-05开放获取
    Microglia Rank signaling regulates GnRH neuronal function and the hypothalamic-pituitary-gonadal axis
    Science (New York, N.Y.) · DOI · Europe PMC
  • 2026-05开放获取
    Novel examples of NMD escape through alternative intronic polyadenylation
    NAR genomics and bioinformatics · DOI · Europe PMC
  • 2026-05开放获取
    Commentary: Clinical evaluation of pediatric olfactory disorders: a review from etiology to management
    Frontiers in allergy · DOI · Europe PMC
  • 2026-05开放获取
    Prokineticin 2 regulates the electrophysiological activity of gonadotropin-releasing hormone neurons via direct signalling in adult female mice
    Frontiers in endocrinology · DOI · Europe PMC
  • 2026-05
    A bibliometric analysis of Kallmann syndrome: trends, hotspots, and future directions
    Orphanet journal of rare diseases · DOI · Europe PMC
  • 2026-05综述开放获取
    Sudden sensorineural olfactory loss: a structured narrative review and proposal for a standardised terminological framework
    Frontiers in surgery · DOI · Europe PMC
  • 2026-05系统综述开放获取
    Neurobiological mechanisms of olfactory dysfunction: a ten-year bibliometric and visualization analysis
    Frontiers in medicine · DOI · Europe PMC
  • 2026-05综述开放获取
    Pediatric endocrine disorders: a review of intracranial findings and appropriate imaging
    Pediatric radiology · DOI · Europe PMC
  • 2026-05系统综述综述开放获取
    Cranial nerves involvement in craniosynostosis: a systematic review
    Child's nervous system : ChNS : official journal of the International · DOI · Europe PMC

在中国开展的临床试验 3L2

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（3 项）
  • 已完成NCT01403532
    Sequential Therapy for Hypogonadotropic Hypogonadism
    IV 期 · 干预性 · 2009/09Shanghai Jiao Tong University School of Medicine
    中国研究中心 1 个：Shanghai
  • 状态未知NCT02880280
    Human Menopausal Gonadotropin Combining With Human Chorionic Gonadotropin Treat Congenital Hypogonadotropic Hypogonadism
    IV 期 · 干预性 · 2016/08Beijing Children's Hospital
    中国研究中心 1 个：Beijing
  • 状态未知NCT03687606
    Efficacy and Safety of Long Term Use of hCG or hCG Plus hMG in Males With Isolated Hypogonadotropic Hypogonadism (IHH)
    IV 期 · 干预性 · 2018/10/18Tongji Hospital
    中国研究中心 1 个：Wuhan

中国境外的在招试验 3L2

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。

荷兰1美国1瑞士1

共 3 项。

  • 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NCT01500447
    Inherited Reproductive Disorders
    观察性 · 2012/04/25National Institute of Environmental Health Sciences (NIEHS)
    美国
  • 招募中NCT01601171
    Genetics of Reproductive Disorders (Including Kallmann Syndrome) and Cleft Lip and/or Palate
    观察性 · 2012/03Centre Hospitalier Universitaire Vaudois
    瑞士

外部标识与链接

OrphanetOMIM:147950OMIM:244200OMIM:308700MONDO:0018800GARD:10771ICD-10 E23.0ICD-11 5A61.2ClinicalTrials.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）