Sonne James, Leslie Stephen W., Lopez-Ojeda Wilfredo
Creighton University School of Medicine
Kaiser Permanente School of Medicine
Kallmann syndrome is a rare congenital form of hypogonadotropic hypogonadism that manifests with partial or complete anosmia. A deficiency in gonadotropin-releasing hormone (GnRH) results in decreased levels of sex steroids, including follicle-stimulating hormone (FSH) and luteinizing hormone (LH), leading to a lack of sexual development and maturity along with the absence of secondary sexual characteristics. Typically, the diagnosis occurs when a child fails to begin puberty, but it can be identified earlier when associated congenital defects raise suspicion or where there is a family history of delayed puberty that suggests a heritable disorder. The connection between hypogonadism and loss of smell was first noted by Spanish pathologist Aurelian Maestre de San Juan in 1856. However, the condition was named after Franz Josef Kallmann, a German-American geneticist, who first described it as a heritable genetic disorder in 1944 based on findings in 3 family clusters. Similar to other hypogonadotropic hypogonadal conditions, Kallmann syndrome is characterized by abnormal or delayed reproductive and sexual characteristics primarily due to a lack of sexual maturation during the typical years of puberty. These signs can include small testicular volume indicative of a lack of testicular development and primary amenorrhea, a failure to start menstruation in women. Poorly defined secondary sexual characteristics can include a lack of pubic hair and underdeveloped mammary glands. Some individuals may also present at birth with micropenis or cryptorchidism (undescended testicles). These traits result from insufficient production of LH and FSH, leading to low levels of testosterone in males and decreased levels of estrogen and progesterone in women. In addition, there are other associated characteristics linked to embryological defects. Kallmann syndrome is defined by its additional presentation of anosmia or hyposmia. Approximately 60% of patients with isolated congenital GnRH deficiency present with an impaired sense of smell, which is characteristic of Kallmann syndrome. Additional characteristics may include cleft lip and palate, unilateral renal agenesis, cryptorchidism, and micropenis. Cerebral impairments, such as central hearing impairment, mirror movements of the hands (synkinesis), and cerebral ataxia, may also be present. Color blindness and ocular window defects have also been observed.
卡尔曼综合征是一种罕见的先天性低促性腺激素性性腺功能减退症，表现为部分或完全嗅觉丧失。促性腺激素释放激素（GnRH）缺乏导致性类固醇水平降低，包括促卵泡生成素（FSH）和促黄体生成素（LH），导致性发育和成熟缺乏以及第二性征缺失。通常，当儿童未能开始青春期时会做出诊断，但当相关的先天性缺陷引起怀疑或有青春期延迟的家族史提示遗传性疾病时，可以更早地识别出来。性腺功能减退与嗅觉丧失之间的联系最早于1856年由西班牙病理学家奥雷利安·梅斯特雷·德·圣胡安发现。然而，该病是以德裔美国遗传学家弗朗茨·约瑟夫·卡尔曼的名字命名的，他于1944年根据对3个家族群体的研究结果首次将其描述为一种遗传性疾病。与其他低促性腺激素性性腺功能减退症一样，卡尔曼综合征的特征是生殖和性特征异常或延迟，主要是由于在青春期的典型年份缺乏性成熟。这些体征可包括睾丸体积小，提示睾丸发育不良，以及原发性闭经，即女性无法开始月经。不明确的第二性征可包括阴毛缺乏和乳腺发育不全。一些个体在出生时也可能出现小阴茎或隐睾症（睾丸未降）。这些特征是由于LH和FSH分泌不足，导致男性睾酮水平低，女性雌激素和孕酮水平降低。此外，还有其他与胚胎学缺陷相关的特征。卡尔曼综合征的定义是伴有嗅觉丧失或嗅觉减退。大约60%的孤立性先天性GnRH缺乏患者存在嗅觉受损，这是卡尔曼综合征的特征。其他特征可能包括唇腭裂、单侧肾发育不全、隐睾症和小阴茎。也可能存在脑部损伤，如中枢性听力障碍、手部镜像运动（联带运动）和脑性共济失调。还观察到色盲和眼窗缺陷。
