Kallmann syndrome is an example of hypogonadism (decreased functioning of the sex hormone-producing glands) caused by a deficiency of gonadotropin-releasing hormone (GnRH), which is created by the hypothalamus. Kallmann syndrome is also known as hypothalamic hypogonadism or gonadotropic hypogonadism, reflecting its disease mechanism.

Features

Kallmann syndrome is characterized by hypogonadotropic hypogonadism with hyposmia (decreased ability to smell) or anosmia (complete inability to smell). It can also be associated with optic problems, such as color blindness or optic atrophy, nerve deafness, cleft palate, cryptorchidism, cleft palate, and movement disorder.

Males present with delayed puberty and may have microphallus. Females present with primary amenorrhea and lack of secondary sexual characteristics, such as breast development.

Diagnosis

The diagnosis is often one of exclusion found during the workup of delayed puberty. The presence of anosmia and microphallus in boys should suggest Kallmann syndrome.

Pathophysiology

Under normal conditions, GnRH travels to the pituitary gland via the tuberoinfundibular pathway, where it triggers production of gonadotropins (LH and FSH). When GnRH is low, the pituitary does not create the normal amount of gonadotropins. The gonadotropins in turn affect the production of hormones in the gonads, so when they are low, the hormones will be low as well.

In Kallmann syndrome, the GnRH neurons do not migrate properly from the olfactory placode to the hypothalamus during development. The olfactory bulb also fails to form or has hypoplasia, leading to anosmia or hyposmia.

Kallman syndrome can be inherited as an X-linked recessive trait, in which case there is a defect in the KAL gene, which maps to chromosome Xp22.3. KAL is a neural cell adhesion molecule, and a defective KAL gene product prevents migration of GnRH neurons.

Treatment

Treatment is directed at restoring the deficient hormones. Males are administered human chorionic gonadotropin or testosterone. Females are treated with estrogen and progestins. To restore fertility in females, GnRH is administered by an infusion pump.

Prognosis

Prevention

Epidemiology

History