This is the most common cause of male hypogonadism with an incidence of approximately 1 in 1000 male births. Individuals have an extra X chromosome. Usually, the karyotype is 47, XXY but variants such as 46, XY/XXY mosaic (1 in 10000 newborn males), multiple X+Y and the so called XX male syndrome are reported.

The supplementary X chromosome is of maternal origin in 60% of cases, and of paternal origin in the remainder. It can result from non-disjunction in either the first or the second meiotic division. There is an increased risk with maternal age but the risk of recurrence in affected parents is low.

Accelerated atrophy of germ cells before puberty results in sterility with small, firm testes. Many patients are tall with relatively long legs. Behavioural disorders and delayed speech development are common. There is considerable variation in the degree of Leydig cell damage. After puberty, some patients show normal muscularity and may present only with infertility. Others may have eunuchoidal body proportions with prominent gynaecomastia.

Testosterone therapy may be used to improve the development of secondary sexual characteristics. Boys tend to be shy, clumsy and have low self esteem. Counselling and encouragement should be given to enable them to become more confident and assertive.

Life span is normal.