Kallmann syndrome combines an impaired sense of smell with a hormonal disorder that delays or prevents puberty.
The hormonal disorder is due to underdevelopment of specific neurons, or nerves, in the brain that signal the hypothalamus. Without these neurons, the hypothalamus cannot properly stimulate the production and release of certain hormones by the pituitary gland. In normal development, the hypothalamus secretes bursts of gonadotropin-releasing hormone (GnRH) at puberty. These bursts of GnRH trigger the pituitary gland to produce hormones that in turn prompt the release of male and female sex hormones by the gonads (testicles and ovaries) and the development of sperm and egg cells. In Kallmann syndrome, the hypothalamus fails to secrete these bursts of GnRH in utero, during infancy, and at puberty.
The early development of the hypothalamus and sense of smell in the human embryo are both affected in Kallmann syndrome. The portion of the hypothalamus that produces GnRH originally forms as part of the nose and migrates during the early stages of embryonic development to join the rest of the hypothalamus. In Kallmann syndrome, both this portion of the hypothalamus and the smell-detecting (olfactory) neurons in the brain do not develop fully.
When a person has the hormone deficiency characteristic of Kallmann syndrome but has a normal sense of smell, the condition is known as normosmic idiopathic hypogonadotropic hypogonadism (nIHH).