Which initial investigations should be performed to confirm a diagnosis of Klinefelter Syndrome?

Initial investigations to confirm a diagnosis of Klinefelter syndrome should include karyotype analysis of the man's chromosomes. This is essential to identify the presence of the extra X chromosome characteristic of Klinefelter syndrome (47,XXY karyotype).

Additionally, semen analysis is important to assess sperm quality and quantity, as men with Klinefelter syndrome often present with severe deficits in semen quality or azoospermia. If severe semen abnormalities or non-obstructive azoospermia are detected, karyotype testing is indicated.

Genetic counselling should be offered before and after karyotype testing to discuss the implications of any detected chromosomal abnormalities.