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Klinefelter’s syndrome

Klinefelter's syndrome is a genetic condition in males caused by the presence of an additional X chromosome.

What is Klinefelter's syndrome?

Klinefelter's syndrome is named after Harry Klinefelter, the medical researcher who originally identified a combination of features found in some males, which included
enlarged breasts, sparse facial and body hair, small testes and low sperm production. This combination of features was first described in 1942, and became known as Klinefelter's syndrome.

Causes and risk factors of Klinefelter's syndrome

Klinefelter's syndrome is caused by the presence of an additional X chromosome. (Chromosomes are thread-like bodies in the cells that carry DNA, the hereditary
material.) Human beings usually have 46 chromosomes, including either two X chromosomes in women (one from each parent); or one X and one Y chromosome
in men (the X chromosome from the mother and the Y from the father). Thus women
have the chromosomal constitution 46,XX and men are 46,XY. Men with Klinefelter's syndrome have the chromosome constitution 47,XXY.

XXY results from an error during meiosis, the division process in the production of
sex cells (sperm or eggs). During meiosis, the 46 chromosomes in the cell divide to
make two sex cells, each containing 23 chromosomes. Each egg contains one X
chromosome; each sperm contains either an X or a Y chromosome. Occasionally, an
additional X chromosome moves into one of the new sex cells, resulting in either an
egg with two X's, or a sperm with both an X and a Y. When a sperm containing both
an X and a Y chromosome fertilises a normal egg with a single X, or a normal sperm
containing a single Y chromosome fertilises an egg with two X's, an XXY male is conceived.

The chance that the additional X chromosome will come from either parent is about
50-50. Older mothers have a slightly increased risk of having an XXY child, but
otherwise it is not known what puts a couple at risk for conceiving a baby with this condition.

About one in 500 to one in 1000 male births are XXY, making it one of the most
common chromosomal abnormalities, and the most common sex chromosome abnormality. However, although the additional X chromosome is common, the set of characteristics it may cause (i.e. Klinefelter's syndrome) is uncommon. Many XXY
males often don't appear to be different, and may never suspect they have an
abnormal chromosomal constitution. Genetic researchers therefore often describe
males with the extra chromosome as “XXY males” rather than “Klinefelter's
syndrome” males.

Over two-thirds of men with this condition have the 47, XXY karyotype (chromosomal constitution), but variations can occur. The most common is XY/XXY mosaicism, in
which some cells have the additional X chromosome and others are normal. In some cases, XY/XXY mosaics have enough normally functioning cells in the testes to be
fertile. Males with two, three or four additional X chromosomes have also been
reported. In these individuals, the Klinefelter's syndrome features may be
exaggerated, with moderate to severe mental disability. In rare instances, a person
may have an additional X and an additional Y chromosome.

Symptoms and signs of Klinefelter's syndrome

Symptoms of Klinefelter's syndrome depend on the life stage:

Infancy and childhood (pre-puberty):

  • Babies usually appear normal at birth.
  • Babies tend to be quiet and rather passive.
  • Toddlers may be shy and reserved, and usually learn to walk later than other children.
  • Boys tend to retain the temperament they had as infants and toddlers: shy, rather passive, and unlikely to take a leadership role.
  • Tend to make friends with other children, but usually only a few at a time.
  • Co-operative and eager to please.
  • Usually underweight
  • Learning disabilities. Although not usually mentally disabled, most XXY males
    have some degree of language impairment. They often learn to speak later than normal and may have difficulty learning to read and write. Although they
    eventually learn to speak normally, most have some degree of language difficulty
    throughout their lives. XXY males usually have particular difficulty with expressive language – the ability to verbally express thoughts and feelings. Their faculty for receptive language (understanding what is said) is close to normal.

Adolescence and adulthood:

  • XXY boys usually enter puberty normally (at age 11-12), but as puberty
    progresses, they may fail to keep pace with other males and secondary sexual characteristics fail to develop fully.
  • In chromosomally normal males, the testicles gradually increase in size, from a
    volume of about 2 ml to about 15 ml. In XXY males the testicles remain at 2 ml
    (usually only 2 cm in length), and do not produce sufficient quantities of
    testosterone, the hormone responsible for development of normal male sexual characteristics.
  • Breast enlargement: the glandular breast tissue may swell, a condition called gynecomastia. Slight breast enlargement is fairly common among normal males entering puberty, and this condition usually disappears after a short time. About a third of XXY boys (slightly more than chromosomally normal boys) develop enlarged breasts in early adolescence. In XXY boys, this condition may be permanent, although only in about 10 percent do the breasts become large enough to require surgery.
  • XXY males are usually infertile, as few sperm develop in the testicles.
  • Lack of facial and body hair.
  • Rounded body type.
  • More likely than other males to be overweight.
  • Tend to be taller than fathers and brothers.
  • Abnormal body proportions (long legs, short trunk).
  • May not be as strong or muscular as males of the same age.
  • May experience fatigue and increased need for sleep.
  • May have little interest in sex.
  • Penis is usually of normal size, although may be smaller than average.
  • Decreased bone mineral density in adults.
  • Simian crease (single crease in the palm).
  • Behavioural problems, including aggression and non-participation in social activities.
  • Tendency to depression.

Not all XXY males will have all or even any of these symptoms, and the severity of
the symptoms varies.

How is Klinefelter's syndrome diagnosed?

Klinefelter's syndrome is diagnosed with chromosome analysis, called karyotyping.
A karyotype is performed either on a sample of blood cells from the person to be diagnosed, or on foetal cells taken from the pregnant mother.

Diagnosis of Klinefelter's syndrome is most likely at the following life stages:

Before birth:

XXY males can be diagnosed prenatally with genetic testing, through amniocentesis or chorionic villus sampling (CVS). In amniocentesis, a sample of the fluid surrounding the foetus is withdrawn, and foetal cells in the fluid are examined for chromosomal abnormalities. In CVS, the foetal cells are taken from the placenta. These procedures are only usually performed when there is a family history of genetic defects, the pregnant woman is older than 35, or when certain other medical conditions require it.


Some XXY males are diagnosed around puberty, when secondary sex characteristics fail to develop or excessive breast development compels them to seek medical advice.


Diagnosis is usually the result of infertility testing. The doctor may notice testicular atrophy and absence of sperm in the ejaculate.

If you have been diagnosed as XXY, do not assume you are infertile without further testing. In a very small number of cases, such as with XY/XXY mosaics, XXY males
have been able to father children. Karyotyping may sometimes fail to identify
XY/ XXY mosaics, and should therefore not be used to predict infertility.

How is Klinefelter's syndrome treated?

Klinefelter's syndrome is treated by dealing with learning difficulties and psychological problems, and providing an appropriate schedule of testosterone treatment.

Treatment for language impairment and learning difficulties

If left untreated, the language impairment experienced by many XXY males can lead
to academic failure and loss of self-esteem. Fortunately, with appropriate help, XXY children are usually able to compensate for their language disability. The chances of
success are greatest if action is taken in early childhood.

Ideally, XXY boys should go to a day-care facility and later a school that can provide
them with the extra attention they require. XXY boys seem to do best in small
classes where teachers can interact with them individually, and to prefer a structured environment with familiar routines. It is important that there is close co-operation
between parents and teachers as to the child's study programme. The following are
some guidelines and techniques used to great benefit by teachers and parents of
XXY boys:

  • Place these students in the front row to reduce distractions.
  • Present information slowly and, if necessary, repeat key points.
  • Do not set tasks that have many small steps. Each step should be presented and completed individually.
  • If XXY boys withdraw from a task they find difficult and lapse into day-dreaming,
    gently regain their attention and focus it on the task.

With specific regard to language acquisition:

  • XXY boys often have decreased immediate auditory recall i.e. they struggle to remember what they have just heard. Help them with this by using visual cues, such as illustrating words with pictures or gestures.
  • XXY boys may have trouble finding the right word to describe an object or situation. There are various techniques to help build vocabulary, including:
    • Providing synonyms, e.g. another word for “happy” is “glad”.
    • Categorising – showing the child that an item belongs to a larger group e.g. apples, oranges and bananas belong to the category “fruit”.
  • To help XXY boys express themselves:
    • Use well designed multiple-choice questions rather than essay-type questions to test what they have learned.
    • Instead of asking an open-ended question, such as “What would you like to work on first?”, offer a choice: “Do you want to do spelling or reading first?”
    • Solicited dialogue: engage the child in conversation through a series of questions. This can also help develop narrative (storytelling) abilities. For example, ask your child what he did at school that day, and follow this with related questions that prompt him to talk about his activities.
    • Modelling: provide the child with examples of how to express himself. For example, if he asks: “Must I put that stuff in the thing?”, you could answer: “Yes, please put the toys in the cupboard.”

Participation in sports and group activities helps improve motor function and muscle development. It is also important to encourage XXY boys to be independent, and not
to overprotect them.

Treatment for psychological problems

XXY males are at risk for depression, especially if they are diagnosed in later
adolescence or adulthood and do not have the benefit of early intervention and
treatment. Adolescence can be difficult for XXY boys. Feeling that they are
“different”, concerns about their masculinity and sexuality, lack of strength and
sporting ability, together with a history of learning disabilities, may damage their
self-esteem. Peers may worsen the situation through teasing or ridicule; teachers
and sometimes parents may have misread learning difficulties as laziness. Language problems and low self-esteem in social settings may have resulted in isolation from
their peers. Some boys may react by becoming depressed and withdrawing socially.

Therefore XXY males, especially if they are diagnosed late, may need psychological counselling in addition to help with learning disabilities.

Testosterone treatment

Most XXY males benefit from testosterone treatment, received as fortnightly
injections. Testosterone doses will be gradually increased over the years, imitating
the increase in testosterone production that occurs during normal development. Men diagnosed in adulthood are also likely to benefit from testosterone treatment.

Advantages of testosterone treatment may include:

  • Increased strength and muscle development
  • Growth of facial and body hair
  • Decreased fatigue and need for sleep
  • Enhanced ability to concentrate, and consequent improvement in academic performance
  • Improved sex drive – can be brought up to normal levels
  • Improved bone strength and development
  • Positive psychological changes and social adjustment. Development of a more masculine appearance helps improve self-confidence and alleviate moodiness, and boosts energy.

Individuals respond to testosterone treatment in different ways. Although most XXY
males benefit from testosterone, some do not. Consult an endocrinologist (a
specialist on hormone disorders) with experience in treating Klinefelter's syndrome
about starting a course of treatment that can best benefit you or your child.

Side-effects of testosterone treatment may include:

  • A minor allergic reaction at the injection site, resembling a mosquito bite. Non-prescription hydrocortisone cream applied to the area should reduce swelling and itching.
  • Benign prostatic hyperplasia (BPH), in which the prostate increases in size, sometimes causing difficulty urinating, “dribbling” after urination, and the need to urinate frequently. BPH is also common in chromosomally normal males, but in XXY males it may begin earlier – after age 40. Consult your doctor about regular prostate examinations.

What is the outcome of Klinefelter's syndrome?

XXY males may be at a slightly increased risk for the following disorders:

  • Autoimmune disorders (in which the immune system attacks the body's tissues), such as type I diabetes, autoimmune thyroiditis, and systemic lupus erythematosus.
  • Pulmonary (lung) disease.
  • Leukemia and Hodgkin and non-Hodgkin lymphoma.
  • Gonadal or extragonadal germinal cell tumours which are tumours of the testis and related structures.
  • Stroke.
  • Varicose veins, which can cause venous ulcers.
  • Thinning of the teeth surface (taurodontism), which can cause early tooth decay.
  • XXY males with enlarged breasts have the same risk of breast cancer as women do – about 50 times that of chromosomally normal males, and need to practise regular breast self examination. Consult your doctor about the need for breast examinations by a medical professional.
  • XXY males who do not receive testosterone treatment may have an increased risk of developing osteoporosis in later life. In this condition, which usually affects post-menopausal women, the bones lose calcium and can break more easily.
  • Depression and other psychological problems.
  • Infertility. The testicular changes that lead to infertility are not preventable and cannot be treated. If you and your partner wish to become parents, seek counselling from your doctor regarding infertility and adoption.

Some studies show that, by their forties, most XXY males have been able to overcome many of their problems. They report increased energy and activity levels, higher work productivity and improved relationships. XXY males do seem less likely to marry than chromosomally normal males, however. That these men overcame
their difficulties is encouraging for others with the condition, particularly those diagnosed in childhood. With early diagnosis, attention to emotional and behavioural problems and learning disabilities, and appropriate testosterone treatment, many more XXY males should enjoy a productive adulthood.

Can Klinefelter's syndrome be prevented?

There is no known way of preventing Klinefelter's syndrome, but early diagnosis and treatment can help manage the condition and prevent some of its complications.

When to call the doctor

Consult your doctor if:

  • Your son's speech development seems to be markedly slower than other children's.
  • Your son fails to develop secondary sexual characteristics.
  • You are concerned that you may have characteristics of Klinefelter's syndrome.

Consult your doctor for referrals to an endocrinologist, mental health specialist
or speech pathologist (specialist in voice and language disorders).

(Reviewed by Prof M. Kibel, Emeritus Professor of Child Health)

The information provided in this article was correct at the time of publishing. At Mediclinic we endeavour to provide our patients and readers with accurate and reliable information, which is why we continually review and update our content. However, due to the dynamic nature of clinical information and medicine, some information may from time to time become outdated prior to revision.