Klinefelter Syndrome: An Underdiagnosed Genetic Disorder

Each person has 23 pairs of chromosomes (46 in total). One of each pair of chromosomes is inherited from the mother and one of each pair is inherited from the father. The 23rd pair of chromosomes is involved in determining gender. The 23rd pair of chromosomes consist of X and/or Y chromosomes.

As the names imply, an X chromosome is shaped like an X, whereas a Y chromosome is shaped like a Y. If a person has two X chromosomes, the person will develop as a female. If a person has an X and a Y chromosome, the person will develop as a male.

In Klinefelter syndrome, the male has at least one extra X chromosome which is why it is known as XXY syndrome or 47,XXY (since there are 47 chromosomes). Because of the extra X chromosome, Klinefelter patients can present with more feminine features such as less hair on the face, armpits, and groin and less masculine features such as small testes which makes it the most common genetic cause of infertility. Many Klinefelter patients tend to be tall with abnormal body proportions. The more X chromosomes present, the more of these abnormal bodily features for males tend to be present.

Klinefelter syndrome is believed to be present in 1 out of every 500 to 1000 male births. While some patients with Klinefelter syndrome show some of signs noted above, the only way to definitely diagnose the condition is by genetic testing.

Klinefelter syndrome is incurable. It is treated with testosterone supplementation at birth (if identified then), which can help normalize body proportions and yield more body hair but it does not treat infertility. Psychological counseling is sometimes used to treat depression and anxiety that results from feeling different. Early identification of Klinefelter syndrome can also help better understand the learning difficulties known to occur in the condition, which typically involves decreased verbal abilities.

In a recent article published in the American Journal of Medical Genetics Part C (Seminars in Medical Genetics), researchers in Denmark published age specific recommendations for medical management in four ranges: ages 0-2, ages 3-10, puberty, and adulthood summarized in a helpful and easy to use table. It is particularly important for health care providers to be more aware of Klinefelter syndrome and these age specific treatment recommendations because as the researchers note, the condition is highly undiagnosed (75% undetected) with only 10% of cases diagnosed before puberty. Typically, Klinefelter syndrome is diagnosed in adulthood during evaluations for infertility. This is troubling because as noted previously, early detection and treatment can improve the lives of these patients.

Suggested reading: Living with Klinefelter Syndrome
 
Reference: Aksglaede L, Link K, Giwercman A, Jørgensen N, Skakkebaek NE, Juul A.(2013). 47,XXY Klinefelter syndrome: Clinical characteristics and age-specific recommendations for medical management. Am J Med Genet C Semin Med Genet.163(1):55-63