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Kallmann综合征(KS)是一种临床和遗传异质性疾病,呈家族性或散发性发病。KS是由胚胎时期嗅球、嗅束的异常发育致使GnRH-1神经细胞不能完成从鼻基板迁移至下丘脑这一过程所引起。GnRH分泌不足导致低促性腺激素性腺功能减退,嗅球、嗅束的异常发育或缺如引起嗅觉丧失。除上述典型症状外,KS患者还可以表现出一些非生殖和非嗅觉表型。KS分子遗传学机制十分复杂,目前只有6个KS致病基因被鉴定。KAL1基因与KS的X连锁隐性遗传模式相关。成纤维细胞生长因子受体1基因(FGFR1/KAL2)和成纤维细胞生长因子8基因(FGF8/KAL6)与常染色体显性遗传模式有关。但是这6个基因的突变只能解释25%~30%的KS病例,提示还有其他KS致病基因有待发现。本文就KS致病基因的研究进展、临床诊断和治疗作一综述。
Kallmann’s syndrome (KS) is a clinical and hereditary heterogeneity with familial or sporadic morbidity. KS is caused by the process of embryonic olfactory bulb and the abnormal development of the olfactory tract, which leads to the inability of GnRH-1 nerve cells to migrate from the nasal substrate to the hypothalamus. Inadequate secretion of GnRH results in hypogonadotropic hypogonadism, abnormal development or absence of the olfactory bulb, olfactory tract, and olfactory loss. In addition to the typical symptoms described above, KS patients may exhibit some non-reproductive and non-olfactory phenotypes. KS molecular genetic mechanism is very complicated, at present, only six KS pathogenic genes were identified. The KAL1 gene is associated with the X-linked recessive inheritance pattern of KS. Fibroblast growth factor receptor 1 (FGFR1 / KAL2) and fibroblast growth factor 8 (FGF8 / KAL6) genes are associated with autosomal dominant patterns. However, the mutation of these six genes can only explain 25% ~ 30% of KS cases, suggesting that there are other KS pathogenic genes to be discovered. This article reviews the progress of KS pathogenicity genes, clinical diagnosis and treatment.