page_title: Kallmann syndrome
section_title: Pathophysiology
hierarchical_section_title: Kallmann syndrome / Pathophysiology
caption_attribution_description: English: The structure of GNRH1 (from PDB 1YY1) (Gonadotropin-releasing_hormone Polski: Gonadoliberyna Nederlands: Gonadotropin-Releasing hormone
context_page_description: Kallmann syndrome is a genetic disorder that prevents a person from starting or fully completing puberty. Kallmann syndrome is a form of a group of conditions termed hypogonadotropic hypogonadism. To distinguish it from other forms of hypogonadotropic hypogonadism, Kallmann syndrome has the additional symptom of a total lack of sense of smell or a reduced sense of smell. If left untreated, people will have poorly defined secondary sexual characteristics, show signs of hypogonadism, almost invariably are infertile and are at increased risk of developing osteoporosis. A range of other physical symptoms affecting the face, hands and skeletal system can also occur.
  The underlying cause is a failure in the correct production or activity of gonadotropin-releasing hormone by the hypothalamus. This results in low levels of the sex hormones testosterone in males or oestrogen and progesterone in females. Diagnosis normally occurs during teenage years when puberty fails to start.
  Lifelong treatment for all sexes is normally required. Hormone replacement therapy is the major form of treatment with the aim to replace the missing testosterone or oestrogen and progesterone.
context_section_description: The underlying cause of Kallmann syndrome or other forms of hypogonadotropic hypogonadism is a failure in the correct action of the hypothalamic hormone GnRH. The term isolated GnRH deficiency (IGD) has increasingly been used to describe this group of conditions as it highlights the primary cause of these conditions and distinguishes them from other conditions such as Klinefelter syndrome or Turner syndrome which share some similar symptoms but have a different etiology. The term hypogonadism describes a low level of circulating sex hormones; testosterone in males and oestrogen and progesterone in females. Hypogonadism can occur through a number of different mechanisms. The use of the term hypogonadotropic relates to the fact that the hypogonadism found in HH is caused by a disruption in the production of the gonadotropin hormones normally released by the anterior pituitary gland known as luteinising hormone (LH) and follicle stimulating hormone (FSH). Failure in GnRH activity can otherwise be due to the absence of the GnRH releasing neurons inside the hypothalamus. HH can occur as an isolated condition with just the LH and FSH production being affected or it can occur in combined pituitary deficiency conditions.
  In the first 10 weeks of normal embryonic development, the GnRH releasing neurons migrate from their original source in the nasal region and end up inside the hypothalamus. These neurons originate in an area of the developing head, the olfactory placode, that will give rise to the olfactory epithelium; they then pass through the cribriform plate, along with the fibres of the olfactory nerves, and into the rostral forebrain. From there they migrate to what will become the hypothalamus. Any problems with the development of the olfactory nerve fibres will prevent the progression of the GnRH releasing neurons towards the brain.
caption: The structure of GNRH1
  (from PDB: 1YY1​)
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