Klinefelter syndrome
Klinefelter syndrome means one extra X chromosome in a boy: instead of the usual XY the make-up is XXY.
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Medicines commonly prescribed for Klinefelter syndrome
For informational purposes only. Always consult a doctor before using any medicine.
Dosage form: GEL, 2% testosteroneActive substance: testosteroneManufacturer: Advanz Pharma LimitedPrescription requiredDosage form: INJECTABLE, Testosterone Propionate 25 mg/mlActive substance: testosteroneManufacturer: Desma Laboratorio Farmaceutico S.L.Prescription requiredDosage form: GEL, 50 mgActive substance: testosteroneManufacturer: Laboratoires Besins InternationalPrescription required
Klinefelter syndrome means one extra X chromosome in a boy: instead of the usual XY the make-up is XXY. It is the commonest chromosome variation in men, occurring in roughly one in five hundred to one thousand newborn boys, and most of the men who have it never find out. The extra X makes nobody less of a man and does not change his sex: sex is set by the Y chromosome, which is still there. What the extra copy does is stop the testicles developing fully, and from that follow the two main consequences: less testosterone and, almost always, disrupted sperm production. Both can be helped, provided somebody knows about them.
Where the extra chromosome comes from
Chromosomes are shared out in pairs when egg and sperm cells are made, and occasionally a pair fails to separate. The egg or the sperm then carries an extra X, and after fertilisation it ends up in every cell of the child. The mistake is a chance one, happens equally often on the mother's and the father's side, and becomes slightly more likely with parental age.
It is worth being clear that Klinefelter syndrome is not inherited. It does not run down the generations, and if a family already has a boy with it, the chance of it happening again in the next child is barely different from anyone else's.
In about one person in ten the extra chromosome is not in every cell but only in some, which is called the mosaic form. Its effects are usually milder and the testicles sometimes keep the ability to make sperm. Rarer still are variants with two or more extra X chromosomes: the more there are, the more marked both the physical features and the learning difficulties become.
How it looks at different ages
The common thread is vagueness. There is no single sign that identifies the syndrome at a glance, and none of the points below is compulsory.
- Babies and toddlers. Slightly weak muscle tone, very bendy joints, later than usual to sit, walk and talk, and sometimes unusually placid. Occasionally a testicle has not descended into the scrotum, or the penis is smaller than usual.
- School years. Language comes to the fore: late to speak, reading and writing are hard work, holding attention is difficult. The boy is often shy, tires quickly and struggles to put feelings into words.
- Adolescence. Taller than the parents would predict, with long arms and legs. Puberty may start on time and then stall: facial and body hair comes in sparsely, muscle is hard to build, fat settles round the hips, the testicles stay small and firm, and in some boys the breasts enlarge.
- Adults. The commonest reason for seeing a doctor is difficulty conceiving. Less often a man comes because of low energy, reduced sex drive, erection problems or low mood.
Why the diagnosis usually arrives late
For most of a lifetime the syndrome gives nothing away, so on various estimates between half and three quarters of men with an extra X are never diagnosed at all. Most often it is found in an adult being investigated for infertility, less often in a teenager whose development is not progressing, and only rarely in a child with delayed speech.
Examination raises the suspicion: small firm testicles in a tall man are a combination not to be walked past. Hormone tests come next. The pattern is characteristic: follicle-stimulating and luteinising hormones are clearly raised, because the pituitary is trying to prod the testicles into action, while testosterone sits low or at the bottom of the range. The diagnosis is confirmed by a karyotype, a blood test in which the chromosomes are counted directly.
Sometimes the extra X is picked up before birth, flagged by a screening blood test in the mother. That result is always checked with an amniotic fluid or chorionic villus sample, because screening suggests rather than proves.
An early diagnosis is not valuable in itself. It is valuable because it buys time: to arrange support at school, to start work on speech, to talk about storing sperm while that is still possible, and not to miss the hormonal and metabolic problems.
Children: what is genuinely possible
This is the commonest reason men come, and the point at which sources usually stop at the word "infertility". The real picture is more complicated and more hopeful.
In the great majority of men with XXY there are no sperm in the ejaculate at all. But sperm production inside the testicle does not usually fail completely or all at once: patches of it carry on working. These can be located during a microsurgical operation in which the surgeon examines the testicular tissue under high magnification and takes the tubules where sperm have survived. In roughly half of cases sperm are obtained, and fertilisation is then possible by injecting a single sperm into an egg. The children are born healthy as often as with any other cause of male infertility.
From this comes a rule worth knowing in advance: testosterone replacement suppresses a man's own sperm production. If having children may ever be on the cards, storing sperm or taking a testicular biopsy is discussed before treatment starts, not after. Teenagers and young men are offered this conversation first, because as the years pass there is less and less usable testicular tissue left.
Testosterone: what it does and does not do
Where testosterone really is lacking, it is replaced. Preparations come as a gel, a skin patch, tablets and injections; the endocrinologist chooses the form and the schedule, or the paediatric endocrinologist in adolescents.
What changes: the voice deepens, body hair grows, muscle is gained and fat lost, bone strengthens, energy and sex drive return and mood often steadies. Treatment usually begins as puberty starts, so that puberty can take its course.
What it does not do: it does not restore fertility but suppresses it; it does not remove breast tissue that has already formed; and it does not replace speech therapy or support with schoolwork. It needs monitoring, with periodic checks of blood, prostate and hormone levels, because it has side effects. It should never be started or altered on your own initiative.
Breast enlargement, if it persists and troubles the man, is dealt with by an operation to remove the glandular tissue.
What to keep an eye on for life
The syndrome by itself does not shorten life, but it raises the likelihood of several conditions, each of them preventable or treatable.
- Bones. A shortage of testosterone thins bone and brings fractures in middle age. Bone density monitoring, enough calcium and vitamin D, and weight-bearing exercise all help.
- Metabolism. Excess weight, type 2 diabetes and raised cholesterol are more common, so blood pressure, glucose and lipids are checked regularly.
- Clots. The tendency to venous thrombosis is increased. Sudden swelling and pain in one leg, and still more so sudden breathlessness or chest pain, mean calling an ambulance at once: in Spain, Italy, Portugal, Poland and Ukraine that is the European number 112.
- Breast. Breast cancer is more frequent in men with this syndrome than in other men, though in absolute numbers it stays rare. It is worth knowing what a warning sign looks like: a hard painless lump, a drawn-in nipple, discharge from it, or a change in the skin.
- Autoimmune disease and the thyroid. Lupus, Sjögren's syndrome, rheumatoid arthritis and an underactive thyroid all turn up somewhat more often than usual.
- A rare but important danger. Teenagers and young men with XXY get germ cell tumours growing in the chest between the lungs more often than other people do. They are very uncommon but move quickly, so a persistent cough, breathlessness, chest pain or a sudden enlargement of the breasts should be shown to a doctor rather than sat out.
Of the things within a man's own control, the usual list works: not smoking, keeping weight down, staying active and keeping alcohol to a minimum. Those measures target precisely the risks listed above.
Speech, schooling and wellbeing
Intelligence in Klinefelter syndrome is generally within the normal range. The difficulties lie elsewhere: it is working with words that suffers. A boy finds it harder to reach for the right phrase, to hold on to what he has heard, and to master reading and writing; clumsiness with fine movements and poor concentration often join in. Anxiety and low mood are more common than among peers, and it is often those, rather than the hormones, that spoil life for an adult man.
All of it responds to help, and the earlier the start the better the outcome. Speech therapy in the preschool years, extra time and support in the classroom, coordination work and, where needed, seeing a psychologist achieve far more than waiting for the child to grow out of it. For an adult it is worth finding a group of people with the same diagnosis: knowing you are not the only one lifts a fair share of the weight.
Online consultation
In an online consultation the doctor will consider whether there is reason to think of Klinefelter syndrome in your case and say which tests to start with: which hormones to measure, what a karyotype is for and how to read results you already have. Parents will be helped to work out what to do about delayed speech or a puberty that has stalled in their son, and which specialists to approach. An adult man with a confirmed diagnosis will be told what to check first, how the conversation about preserving fertility is framed, and in what order to tackle testosterone, bone and metabolism.
This material is for information only and does not replace medical advice.
Consult with a doctor about Klinefelter syndrome
Discuss your symptoms and possible next steps with a doctor online.
Online doctors for Klinefelter syndrome
Discuss your symptoms and possible next steps for Klinefelter syndrome with a doctor online.
