Klinefelter syndrome is a genetic disorder that affects one in every 660 men. Specifically, this condition means that people who have it have an extra X chromosome, which can come from either the father or the mother. Generally, the genes on the extra chromosome are usually inactivated, but those that are not are the cause of the syndrome.
This type of syndrome is one of the least diagnosed (only 25% of cases are diagnosed), and when it is diagnosed, it is usually at an advanced age. In Spain alone, the average age of diagnosis is 29 years old. In addition, it is associated with increased morbidity, leading to a decrease in life expectancy of up to two years due to various associated diseases.
Consequences of having Klinefelter syndrome
People with this syndrome have small testicles, primary hypogonadism (lack of sperm due to a disorder in the testicles), and cognitive impairment that mainly affects language processing; therefore, it is normal for children with Klinefelter syndrome to need speech therapy and suffer from learning difficulties. And due to hypogonadism, changes in body composition can occur and type 2 diabetes can develop due to metabolic syndrome.
The only medical treatment currently available involves the administration of testosterone to alleviate the consequences of hypogonadism and reduce the most common morbidity.
Frequency of characteristics associated with Klinefelter syndrome
| Characteristic | Frequency (%) |
| Infertility | 90-99 |
| Small testicles (combined size <6mL) | More than 95% |
| Azoospermia (absence of sperm in semen) | More than 95% |
| Learning difficulties | More than 75% |
| decreased testosterone levels | Between 60 and 85% |
| Decreased facial and public hair | Around 50% |
| Gynecomastia | Between 38-75% |
| Increased height | Over 30% |
| Type 2 diabetes | Between 10 and 39% |
| Psychiatric disorders | 25% |
| Congenital malformations | 18% |
| Breast cancer | 50 times higher risk |
| Fractures | 2 to 40 times higher risk |
Why does Klinefelter syndrome occur?
The genetic background of this syndrome is based on the presence of an extra X chromosome. In the case of women, they already have two X chromosomes, but one of these is inactivated, expressing only a few genes that are not inactivated. In the case of this syndrome, exactly the same thing happens. Of these genes, the only one that has been shown to influence the phenotype of Klinefelter syndrome is the one containing the short stature homeobox (SHOX) located in the pseudoautosomal region 1 on Xp. This gene is also related to bone growth delays in Turner syndrome and Leri-Weill dyschondrosteosis. In addition to being related to accelerated growth in Klinefelter syndrome.
Can you have children if you have this syndrome?
Although men with Klinefelter syndrome are considered infertile, recent studies have shown that with modern technology such as testicular sperm extraction followed by intracytoplasmic sperm injection, fatherhood is possible. However, many other couples choose adoption or the use of donors to become parents.
The results obtained using testicular sperm extraction technology show a 66% recovery of sperm, with approximately 45% resulting in birth.
Diabetes and Klinefelter syndrome
The relationship between diabetes and Klinefelter syndrome has been known for more than 50 years. In a study led by Nielsen in 1979, a higher prevalence (39%) of impaired oral glucose tolerance was described in diabetics, while other studies found decreased insulin sensitivity and elevated fasting insulin levels in seven patients with the syndrome.
Phenotype related to the syndrome
The phenotype of this syndrome presents a wide range of characteristics, making it impossible to define. This could be one of the reasons why the syndrome is significantly underdiagnosed, with less than 25% of adult males diagnosed. However, among the characteristics of these individuals is accelerated growth from childhood, tending to be taller than average. This increase in final height is mainly due to abnormally long legs, with abdominal obesity also present.
Groth, K. A., Skakkebæk, A., Høst, C., Gravholt, C. H., & Bojesen, A. (2013). Clinical review: Klinefelter syndrome–a clinical update. The Journal of clinical endocrinology and metabolism, 98(1), 20–30. https://doi.org/10.1210/jc.2012-2382