15th April 2024

Klinefelter syndrome

Background

Epidemiology

Klinefelter’s is the most common cause of congenital primary hypogonadism associated with chromosomal abnormalities occurring in 1 out of every 500-700 male neonates with a prevalence at adulthood of 1 out of 2500 males the lower prevalence of Klinefelter’s at adulthood is thought to be due to the condition being ignored or underdiagnosed.

Aetiology

Klinefelter’s occurs due to one or more extra X chromosomes as a result of either maternal or paternal meiotic non-disjunction, 90% of Klinefelter’s occurs due to the 47, XXY karyotype with the remaining 10% due to mosaic Klinefelter’s (47, XXY/46, XY) with some patients having more than one extra X chromosome (48, XXXY/49XXXXY).

Presentation

Patients with mosaic Klinefelter’s syndrome tend to have a milder form of the condition and if the karyotype located in the testis is of the 46, XY type spermatogenesis is normal, patients with more than one extra copy of the X chromosome tend to have a more severe presentation.  The characteristic phenotype associated with Klinefelter’s includes:

• Small firm testis
• Above average height
• Erectile issues
• Sparse male-pattern body hair
• Bilateral gynaecomastia
• Infertility

References

• Marcelli M, Mediwala SN. Male hypogonadism: a review. J Investig Med. 2020;68(2):335-56.
• Bojesen A, Juul S, Gravholt CH. Prenatal and postnatal prevalence of Klinefelter syndrome: a national registry study. J Clin Endocrinol Metab. 2003;88(2):622-6.
• Morris JK, Alberman E, Scott C, Jacobs P. Is the prevalence of Klinefelter syndrome increasing? Eur J Hum Genet. 2008;16(2):163-70.
• Nieschlag E. Klinefelter syndrome: the commonest form of hypogonadism, but often overlooked or untreated. Dtsch Arztebl Int. 2013;110(20):347-53.