Kallmann syndrome (congenital hypogonadotropic hypogonadism with anosmia) is a developmental genetic disease primarily defined by delayed or absent puberty and an altered sense of smell that is either absent or reduced. Four types of Kallmann syndrome have been identified, and they are distinguished by their genetic cause.

More prevalent in males. Kallmann syndrome type 1 is the more commonly occurring form.

Kallmann syndrome type 1 is specifically caused by gene mutations of ANOS1. Kallmann syndrome type 2 is caused by gene mutations occurring in the FGFR1 gene. Mutations in the PROKR2 and PROK2 genes are responsible for types 3 and 4 of Kallmann syndrome. All types of Kallmann syndrome present with hypogonadotropic hypogonadism and altered sense of smell. However, other clinical features, such as the midline defect cleft palate, only occur in types 1 and 2. Kallmann syndrome type 1 is X-linked and has an autosomal recessive form of inheritance. Other types of Kallmann syndrome can be inherited in an autosomal dominant pattern.

The clinical presentation of Kallmann syndrome is variable. Male patients with hypogonadotropic hypogonadism usually present with micropenis and undescended testes at birth. At puberty, female patients usually will not begin menstruation and lack breast development. For some patients, puberty is either incomplete or postponed. Other signs and symptoms include unilateral renal agenesis, cleft lip, abnormal eye movements, hearing loss, and dental malformations. Less commonly, patients may present with bimanual synkinesis.

Treatment options are available to induce puberty and fertility, help patients achieve fertilization and virilization, and assist with reproductive development. Options include hormonal replacement therapy, human chorionic gonadotropin injections, follicle-stimulating hormone, estrogen, and pulsatile gonadotropin-releasing hormone administration, or exogenous gonadotropins. There is no available therapy for anosmia.

Kallmann syndrome is not serious or life-threatening. If the patient is treated with hormonal therapy, pubertal fertilization and virilization will occur. It may be more challenging for male patients with cryptorchidism to achieve fertility.