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What Is Klinefelter Syndrome?

Klinefelter syndrome is a common genetic chromosomal condition that occurs when a boy is born with an extra copy of the X chromosome.

Klinefelter syndrome can affect both physical and cognitive development.

According to the National Human Genome Research Institute, Klinefelter syndrome is found in about 1 out of every 500 to 1,000 newborn males, making it one of the most common chromosomal conditions. The Association for X and Y Chromosome Variations (AXYS), a group that focuses on Klinefelter syndrome and other similar conditions, estimates the Klinefelter occurrence at 1 in 600 male births.

Klinefelter Syndrome Causes

Klinefelter syndrome occurs as the result of a random genetic error during the formation of the egg or sperm at or soon after conception, according to MedlinePlus.

The syndrome is not inherited through the parents' genes or the result of something the parents did or did not do.

Women who become pregnant after 35 years of age have a slightly increased risk of having a boy with Klinefelter syndrome, per the National Human Genome Research Institute.

People normally have 46 chromosomes in each cell. Two of those 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male or female sex characteristics.

Females usually have two X chromosomes, while males have one X chromosome and one Y chromosome.

However, Klinefelter syndrome occurs because of one extra copy of the X chromosome in each cell (XXY), notes the Mayo Clinic. Because Klinefelter syndrome involves an extra X chromosome, it is also sometimes referred to as 47,XXY syndrome, notes AXYS.

Some males with Klinefelter syndrome have the extra X chromosome only in some of their cells. When this occurs it is called mosaic Klinefelter syndrome, per the Mayo Clinic.

While rare, a similar but more severe condition known as 48,XXXY can occur when a male has two extra copies of the X chromosome, according to AXYS.

Klinefelter Syndrome Symptoms

The most common symptom of Klinefelter syndrome is infertility, which often isn't noticed until adulthood, notes the Mayo Clinic.

Klinefelter syndrome adversely affects testicular growth, resulting in smaller than normal testicles, which often leads to low production of testosterone.

Although most men with Klinefelter syndrome produce little or no sperm, reproductive procedures may make it possible for some men with the condition to father children.

The effects of Klinefelter syndrome vary from person to person, and signs and symptoms of the syndrome can appear differently at different ages, according to the Mayo Clinic.

Symptoms in babies:

  • Weak muscles
  • Slow motor development of things like sitting up, crawling, and walking
  • Speech delay
  • Docile personality
  • Testicles that haven't descended into the scrotum
  • Symptoms in boys and teenagers:

  • Taller than average stature
  • Longer legs, shorter torso, and broader hips
  • Absent, delayed, or incomplete puberty
  • Less-muscular bodies and less facial and body hair after puberty
  • Small, firm testicles
  • Small penis
  • Enlarged breast tissue
  • Weak bones
  • Low energy levels
  • Shyness
  • Difficulty expressing feelings or socializing
  • Problems with reading, writing, spelling, or math
  • Difficulty being attentive
  • Symptoms in men:

  • Infertility
  • Small testicles and penis
  • Taller than average stature
  • Weak bones (osteoporosis)
  • Decreased facial and body hair
  • Enlarged breast tissue
  • Decreased sex drive
  • Complications

    Men with Klinefelter syndrome may be at increased risk for the following:

  • Varicose veins and other problems with blood vessels
  • Breast cancer and cancers of the blood, bone marrow, or lymph nodes
  • Lung disease
  • Autoimmune disorders, such as type 1 diabetes and lupus
  • Belly fat, which can lead to other health problems
  • Testosterone replacement therapy can reduce the risk of the health problems listed above, especially when therapy is started at the onset of puberty.
  • Klinefelter Syndrome Diagnosis

    If you suspect that you or your son may have Klinefelter syndrome, your doctor will examine your (or your son's) genital area and chest, as well as conduct tests to check reflexes and mental functioning.

    Additionally, the following tests are used to diagnose Klinefelter syndrome, per the Mayo Clinic:

    Chromosomal Analysis Also called karyotype, this involves drawing a small sample of blood, which is sent to a lab to check the shape and number of chromosomes.

    Hormone Testing This can be done through blood or urine samples and can detect if abnormal sex hormone levels — a sign of Klinefelter syndrome — are present.

    Klinefelter Syndrome Treatment

    While there is no cure for sex chromosome changes caused by Klinefelter syndrome, treatments can help minimize effects, especially when they're started early. Treatment may include the following:

    Testosterone replacement therapy Since males with Klinefelter syndrome don't produce enough testosterone, undergoing testosterone replacement therapy at the onset of puberty can allow a boy to undergo the body changes that normally occur at puberty, such as developing a deeper voice, growing facial and body hair, and increasing muscle mass and penis size.

    Testosterone therapy can also improve bone density and reduce the risk of fractures, but it will not enlarge the testicles or help with infertility.

    Testosterone may be given as an injection or with a gel or patch on the skin.

    Fertility Treatments Intracytoplasmic sperm injection (ICSI) can help men with minimal sperm production by removing sperm from the testicle and injecting it directly into a woman's egg.

    Breast Tissue Removal For those who develop enlarged breasts, excess breast tissue can be removed with plastic surgery.

    Educational Support Teachers, school counselors, or school nurses may be able to help with finding extra support for learning.

    Speech and Physical Therapy These can help overcome problems with speech, language, and muscle weakness.

    Psychological Counseling Whether from a family therapist, counselor, or psychologist, counseling can help people with Klinefelter syndrome work through emotional issues related to puberty, young adulthood, and infertility.


    New Solutions To Reproductive Problems Related To Chromosomal Variations

    Approximately one in every 500 to 650 baby boys is born with an extra X chromosome, a variation in their genetic code that until a few years ago was thought to result in infertility in all cases. However, this is no longer the case.

    As recently as 10 years ago, all men born with an extra X chromosome—a condition whose classic symptoms are known as Klinefelter syndrome—were thought to be infertile. Now, new research at NewYork-Presbyterian/Weill Cornell, led by Dr. Peter Schlegel, has pioneered a surgical approach—a combination of TESE (testicular sperm extraction) and IVF (in vitro fertilization)—that enables these men to father healthy children approximately 40 percent of the time it is employed.

    "Our current research in the laboratory focuses on understanding the mechanism by which the presence of an additional X chromosome affects sperm production and testosterone synthesis in males with Klinefelter syndrome. These critical and unique studies will allow us to provide improved treatment and management recommendations based on solid understanding of underlying pathophysiology," says Dr. Darius A. Paduch, assistant professor of urology and reproductive medicine at Weill Cornell Medical College and assistant attending urologist at NewYork-Presbyterian/Weill Cornell.

    Most individuals have a total of 46 chromosomes. Commonly, men have one X and one Y chromosome; and women have two X chromosomes. But this is not true for everyone. The most common variation is 47XXY in boys and Trisomy X in girls. Without proper interventions, boys born with an extra X chromosome are at a significantly heightened risk of developing the signs and symptoms of Klinefelter syndrome as adults. Unlike other genetic syndromes such as Down's or Fragile X, comparatively little is known about X and Y chromosome variations.

    Dr. Paduch, who leads NewYork-Presbyterian/Weill Cornell's translational research into the molecular biology and genetics of 47XXY and Klinefelter syndrome, has assembled a diverse group of scientists from Cornell-Ithaca and Rockefeller University to create a center of excellence in research on Klinefelter syndrome.

    Robert Shelton, chairman of the Board of Directors of KS&A said: "There is a high likelihood that research into these chromosomal variations will make substantial contributions to knowledge about breast cancer, learning disabilities and other seemingly unrelated phenomena as more is discovered concerning the relevance of genes located on the X and Y chromosomes."

    This information was presented at arecent conference hosted by NewYork-Presbyterian Hospital/Weill Cornell Medical Center and advocacy organization KS&A focused on raising awareness of the condition and the recent availability of treatments for both children and adults.


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