Klinefelter syndrome refers to a collection of characteristics in males that are caused by having two or more X chromosomes (instead of a normal chromosomal makeup of 46,XY, people with Klinefelter syndrome usually have 47,XXY) . Although it’s the most common chromosomal disorder affecting men, limited awareness among the public and health professionals contributes to many men being undiagnosed. The effects of Klinefelter syndrome also vary significantly between different people. In some individuals, the signs and symptoms of Klinefelter syndrome can be so that they, their parents, partners, and their doctors may not even realise they have the condition.
Klinefelter syndrome is beginning to be picked up more often, because of changes to prenatal screening. The prenatal diagnosis rate of 47,XXY increased from about 1 in 10,000 births in 2005 to more than 4 in 10,000 births in 2020. However, prenatal testing for Klinefelter syndrome is not routine, because the balance between the pros and cons is not well understood.
Prenatal screening of Klinefelter syndrome
Klinefelter syndrome is diagnosed by examining someone’s karyotype, which is done using a small sample of blood or other tissue. Testing for 47,XXY during pregnancy is optional and should be discussed with your doctor, midwife or genetic counsellor.
After 10 weeks of pregnancy, non-invasive prenatal testing (NIPT) can look at small pieces of DNA in a sample of the mother’s blood, to determine the likelihood that her fetus has one of the most common chromosome conditions: trisomy 21 (Down syndrome), trisomy 18 or trisomy 13. There is also an option to screen for sex chromosome aneuploidies (conditions in which individuals have an abnormal number of sex chromosomes) which can identify Klinefelter syndrome, Turner syndrome (45,X), Jacobs syndrome (47,XYY), Triple X and XXYY.
NIPT might show your baby has a high risk of Klinefelter syndrome, but this is not confirmation. In some cases, high-risk results for 47,XXY may represent ‘false positives’. Chorionic villus sampling (CVS) or amniocentesis can diagnose Klinefelter syndrome. These diagnostic tests provide a more accurate result as they are generally directly testing the fetus. The procedures for CVS and amniocentesis carry a very small risk of miscarriage.
Genetic counselling for Klinefelter syndrome
Women with a high-risk screening result should have access to genetic counselling services for support. Genetic counsellors have specialist knowledge in human genetics, counselling and communication, and are experts at making complex medical information understandable. They provide practical, up-to-date information to individuals and families about genetic conditions like Klinefelter syndrome and assist them in making informed decisions that are right for them and their families.
A prenatal diagnosis of Klinefelter syndrome can be challenging for families, the type of medical professional providing counselling can impact the outcome of the pregnancy. Healthcare providers should have an up-to-date understanding of the condition, but many might not. If you aren’t referred to a genetic counsellor, you can ask to be.
 Loughry, L, Pynaker, C, White, M, Halliday, J, Hui, L. (2022) State-wide increase in prenatal diagnosis of klinefelter syndrome on amniocentesis and chorionic villus sampling: Impact of non-invasive prenatal testing for sex chromosome conditions. Prenat Diagn
 Turriff A, Macnamara E, Levy HP, et al. (2016) The impact of living with Klinefelter syndrome: a qualitative exploration of adolescents and adults. J Gen Counseling