Kallmann's syndrome

Kallmann's syndrome is a recognised cause of delayed puberty secondary to hypogonadotropic hypogonadism. It is usually inherited as an X-linked recessive trait. Kallmann's syndrome is thought to be caused by failure of GnRH-secreting neurons to migrate to the hypothalamus.

The clue given in many questions is lack of smell (anosmia) in a boy with delayed puberty.

Features

• 'delayed puberty'
• hypogonadism, cryptorchidism
• anosmia
• sex hormone levels are low
• LH, FSH levels are inappropriately low/normal ^^
• patients are typically of normal or above-average height

Cleft lip/palate and visual/hearing defects are also seen in some patients

Management

• testosterone supplementation
• gonadotrophin supplementation may result in sperm production if fertility is desired later in life

^^ Low FSH/LH and low testosterone is correct. In normal physiology, the hypothalamus produces GnRH, GnRH then stimulates LH and FSH production from the anterior pituitary, and FSH/LH go on to stimulate testosterone from the testes. Kallman's syndrome is caused by a failure of the embryonic development of olfactory nerve fibres, which in turn prevents the normal embryonic migration of nerves that produce gonadotrophin releasing hormone (GnRH) from the olfactory region to the hypothalamus. Accordingly, the absence of GnRH producing cells in Kallman's syndrome means there is no downstream stimulation of LH/FSH production and therefore no stimulation of testosterone production. Further, failure of olfactory nerve development causes a reduced or absent sense of smell, which is characteristic for Kallman's syndrome.