Common Questions about Klinefleter syndrome

What is Klinefelter Syndrome?

Klinefelter syndrome is a genetic condition in boys and men who have an extra X chromosome. 

Klinefelter’s, 47,XXY, XXY, XXY syndrome, and KS are all different names for Klinefelter syndrome.

Klinefelter syndrome is part of a bigger group of genetic conditions called sex chromosome aneuploidies (SCAs). The X and Y chromosomes are called sex chromosomes; individuals typically have two sex chromosomes. “Aneuploidy” means an abnormal number. So sex chromosome aneuploidies include all conditions that have one or more than two X and/or Y chromosomes. There are many other names that SCAs may go by, such as X&Y chromosome variations, X&Y variations, sex chromosome variations, etc. 

There are some other SCA conditions such as 48,XXYY, 48,XXXY, and 49,XXXXY that are sometimes also called “variants” of Klinefelter syndrome. These conditions share some of the features of XXY such as testicular failure in adolescence and tall stature, however, they are more commonly associated with learning/cognitive disabilities, language difficulties, and sometimes more complex medical problems.

Klinefelter syndrome has been referred to as all of these things, and others. The genetic condition is the most neutral of these terms. 

Klinefelter syndrome is caused by having many extra genes on the additional X chromosome. We do not know exactly how these genes lead to the features of the condition.

Dr. Harry Klinefelter was a medical student when he described several young men with specific physical features in a medical paper in 1942. These features became known as “Klinefelter syndrome”. In 1959, Dr. Patricia Jacobs found out that the reason these men had these physical features was because of an extra X chromosome. 

Studies show 1 in 500-1000 males have an extra X chromosome.

Historically, studies have shown that ~2/3 of boys with KS were never appropriately diagnosed. These numbers may be decreasing as genetic testing, especially prenatal genetic testing, becomes more common.  

Klinefelter syndrome is diagnosis by a test called a karyotype or chromosome analysis on blood or other tissue type. Sometimes other genetic tests can pick up Klinefelter syndrome as well. 

Infancy/Toddlerhood

Often no signs or symptoms are noticeable in infants and young boys

  • Low to normal muscle tone
  • Difficulty with breastfeeding
  • Easy-going baby
  • Mild delay in milestones
  • Undescended testes or small penis size
  • Allergies / Recurrent respiratory infections / Asthma

Childhood

  • Kind, loving, eager-to-please personality
  • Difficulty with language-based academics (reading, writing, reading comprehension)
  • Social immaturity relative to peers
  • Attention or focus difficulties
  • Anxiety
  • Challenges with motor planning or coordination, handwriting 
  • Low energy or fatigue
  • Sensory sensitivities or becoming easily frustrated
  • Allergies / Recurrent respiratory infections / Asthma

Adolescence and Adulthood

  • Taller stature
  • Puberty differences: Puberty usually starts at a normal time and penis size and pubic hair development are usually normal, so differences can be hard to notice. Testicles stop growing or get smaller in mid-puberty and produce less testosterone, which can lead to less facial hair, lower muscle mass, and breast tissue development. Treatment with testosterone can help prevent or treat these problems if they occur.  
  • Infertility
  • Increased fat tissue on hips and abdomen
  • Abnormal cholesterol, pre-diabetes or diabetes
  • Difficulty with higher level language skills and social communication skills such as difficulty describing events or thoughts in clear detail, “reading between the lines” in conversations, taking things too literally, or maintaining conversations. 
  • Anxiety and/or depression
  • Attention or focus difficulties, difficulties with organization and planning
  • Academic challenges in reading and writing, reading comprehension
  • Low energy or motivation, fatigue
  • Tremor (shakiness) in hands
  • Strengths in visual-spatial tasks, creativity, and art 
  • Strengths in science/technology/engineering/math disciplines

Klinefelter syndrome is a spectrum, with some individuals affected very little and others reporting Klinefelter syndrome has a significant impact on their lives. This variability is one of the most important things to know about Klinefelter syndrome – not all males with Klinefelter syndrome will have all of the signs or symptoms described above. Some may have very few developmental or learning challenges. However, almost all will show small testicular size in adolescence and pubertal differences.

Klinefelter syndrome is best treated with a multidisciplinary team that has experience with individuals with KS. Many of the “classic” signs and symptoms of Klinefelter syndrome can be prevented or treated. Management can include developmental therapies (i.e., physical, occupational, speech therapy), academic supports, healthy lifestyle habits (diet, activity, sleep), treatments for mental health/behavioral difficulties if needed, and testosterone treatment. 

Many boys and men with Klinefelter syndrome have excellent quality of life and very positive outcomes, including being in successful relationships and employment. Most men with Klinefelter syndrome live independently without assistance. However, studies do suggest that men with Klinefelter syndrome may have more challenges maintaining relationships or work compared to others. Quality of life can be affected by physical and mental health conditions. It is important to get support from a team of specialists that understand Klinefelter syndrome to appropriately treat these conditions and achieve positive quality of life.