Kallmann syndrome
Kallmann syndrome (KS) 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 (anosmia) or a reduced sense of smell.[1][2][3] 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.[1] A range of other physical symptoms affecting the face, hands and skeletal system can also occur.[2]
Kallmann syndrome
Kallmann's hereditary anosmia
Absent or delayed puberty, infertility, inability to smell
Lifelong
1:30,000 (males), 1:125,000 (females)
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.[3]
Lifelong treatment for both sexes is normally required. Hormone replacement therapy (HRT) is the major form of treatment with the aim to replace the missing testosterone or oestrogen and progesterone. Specialised fertility treatments are also available.[4]
The condition is more commonly diagnosed in males than in females.[5] A 2011 study of the Finnish population produced an estimated incidence of 1 in 48,000 people overall, with 1 in 30,000 for males and 1 in 125,000 for females.[6] Kallmann syndrome was first described by name in a paper published in 1944 by Franz Josef Kallmann, a German-American geneticist.[7][8] The link between anosmia and hypogonadism had already been noted by Spanish doctor Aureliano Maestre de San Juan in 1856.[9][10]
Prognosis[edit]
Reversal of symptoms has been reported in between 10% and 22% of cases.[38][2]
Reversal cases have been seen in both KS and normosmic CHH but appear to be less common in cases of KS (where the sense of smell is also affected). Reversal is not always permanent and the precise genetic causes are not yet fully understood.[39]
Epidemiology[edit]
The epidemiology of Kallmann syndrome is not well understood. Individual studies include a 1986 report reviewing medical records in the Sardinian army which found a prevalence of 1 in 86,000 men[40] and a 2011 report from Finland which found a prevalence of 1:30,000 for males and 1:125,000 for females.[41]
Kallmann syndrome occurs about 4 times more often in males than females, but is only 2.5 times more common among males in familial cases.[40][41]
The terminology used when describing cases of HH vary and can include:
Research[edit]
Kisspeptin is a protein that regulates the release of GnRH from the hypothalamus, which in turn regulates the release of LH and, to a lesser extent, FSH from the anterior pituitary gland. Kisspeptin and its associated receptor KISS1R are known to be involved in the regulation of puberty. Studies have shown there is potential for kisspeptin to be used in the diagnosis and treatment of certain cases of Kallmann syndrome and CHH.[44][45]