gonadotropins LH and FSH. Hypogonadism due to low levels of testosterone in men or oestrogen/progesterone in women. Infertility. Non-reproductive features Total lack of sense of smell (anosmia) or markedly reduced sense of smell (hyposmia). This is the defining feature of Kallmann syndrome; it is not seen in other cases of HH. Approximately 50% of HH cases occur with anosmia and can be termed as Kallmann syndrome. Cleft palate, cleft lip or other midline cranio-facial defects. Neural hearing impairment Absence of one of the kidneys (unilateral renal agenesis) Skeletal defects including split hand/foot (ectrodactyly), shortened middle finger (metacarpal) or scoliosis Manual synkinesis (mirror movements of hands) Missing teeth (hypodontia) Poor balance or coordination due to cerebral ataxia. Eye defects such as coloboma or ptosis. Increased incidence of color-blindness The exact genetic nature of each particular case of KS/HH will determine which, if any, of the non-reproductive features will occur. The severity of the symptoms will also vary from case to case. Even family members will not show the same range or severity of symptoms. KS/HH is most often present from birth but adult onset versions are found in both males and females. The hypothalamic-pituitary-gonadal axis (HPG axis) functions normally at birth and well into adult life, giving normal puberty and normal reproductive function. The HPG axis then either fails totally or is reduced to a very low level of GnRH release in adult life with no obvious cause (e.g. a pituitary tumour). This will lead to a fall in testosterone or oestrogen levels and infertility. Functional hypothalamic amenorrhoea is seen in females where the HPG axis is suppressed in response to physical or psychological stress or malnutrition but is reversible with the removal of the stressor. Some cases of KS/HH appear to reverse during adult life where the HPG axis resumes its normal function and GnRH, LH, and FSH levels return to normal levels. This occurs in an estimated 10 to 22% of people, primarily normosmic CHH cases rather than KS cases and only found in people who have undergone some form of testosterone replacement therapy. It is only normally discovered when testicular volume increases while on testosterone treatment alone and testosterone levels return to normal when treatment is stopped. This type of KS/HH rarely occurs in cases where males have had a history of un-descended testes. Affected individuals with KS and other forms of HH are almost invariably born with