Klinefelter Syndrome: An Extra X Makes the Diagnosis

Klinefelter syndrome is a genetic condition marked by a difference in the number of sex chromosomes in those assigned male at birth. Usually there is one copy of the X chromosome and one copy of the Y chromosome in each cell. In those with Klinefelter syndrome, each cell instead has two copies of the X chromosome and one copy of the Y chromosome.

Klinefelter syndrome is very common, affecting approximately 1 in 600 males, although many individuals may go undiagnosed.

What Are the Symptoms and Signs of Klinefelter Syndrome?

Those with Klinefelter syndrome may have very few symptoms or may have many. Some individuals are not diagnosed until adulthood, such as during a work-up for infertility. Others may be diagnosed during childhood, such as during a work-up for puberty concerns or small testes.

From an endocrine perspective in addition to infertility and puberty concerns, Klinefelter syndrome can be associated with tall stature, gynecomastia (breast development), and osteoporosis (weak bones). Those with Klinefelter syndrome can have neurodevelopmental differences such as learning difficulties and behavioral concerns. There also may be a relatively higher long-term risk of cardiovascular problems, autoimmune diseases, and certain cancers.

How Is Klinefelter Syndrome Diagnosed?

A blood test called a karyotype is used to diagnose Klinefelter syndrome. A karyotype counts the number of chromosomes in each cell. A karyotype can be done at any age, from infancy to adulthood. Additionally, as genetic testing is now more common during pregnancy, some children with Klinefelter syndrome may be diagnosed before they are born.

What Is the Treatment for Klinefelter Syndrome?

While there is currently no way to change the number of sex chromosomes in each cell, individual symptoms associated with Klinefelter syndrome can be treated. Some interventions may include:

• Testosterone injections for pubertal development and adult hormone replacement
• Neurodevelopmental testing
• Additional educational support in school
• Assisted reproductive technology including testicular sperm extraction

It is important that individuals with Klinefelter syndrome follow up with a pediatrician or primary care provider to help coordinate care. There are also national and international support groups for individuals and their families.