Turner and Klinefelter Syndromes
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Direct answer
Turner syndrome and Klinefelter syndrome are sex-chromosome disorders confirmed by karyotype. Turner is a female with 45,X or a mosaic or structurally altered X, showing short stature, ovarian failure and a Barr-body-negative nucleus. Klinefelter is a male with 47,XXY, showing small testes, primary hypogonadism, infertility and one Barr body.
What you must remember
- Turner karyotype: 45,X in about half of cases; mosaics and isochromosome Xq account for much of the rest, and any Y-chromosome material prompts gonadectomy because of gonadoblastoma risk.
- Turner phenotype: short stature, webbed neck, shield chest, cubitus valgus and a short fourth metacarpal, with streak gonads and raised gonadotropins.
- Turner associations: bicuspid aortic valve, coarctation of the aorta, horseshoe kidney, autoimmune hypothyroidism and sensorineural hearing loss.
- Klinefelter karyotype: 47,XXY is the commonest form; mosaic 46,XY/47,XXY gives a milder picture, and one Barr body is present.
- Klinefelter phenotype: tall stature with long limbs, small firm testes, gynaecomastia, azoospermia, low testosterone with raised FSH and LH, and frequent learning difficulties.
- Klinefelter associations: type 2 diabetes, osteoporosis, venous thromboembolism, autoimmune disease and breast cancer, each above the general male risk.
- Management: growth hormone improves height in Turner, oestrogen induces puberty, and testosterone replaces androgen in Klinefelter after sperm retrieval has been discussed.
Worked example: a short girl who has not started puberty
A 14-year-old girl is referred for short stature. Her height is below the third centile, her growth velocity has slowed and breast development has not started.
- Examine for stigmata: Examination shows a webbed neck, a broad chest with widely spaced nipples and cubitus valgus.
- Check the hormones: FSH and LH are raised with low oestradiol, which points to gonadal dysgenesis, so a peripheral blood karyotype is the next step.
- Count metaphases: When mosaicism is suspected, counting around thirty metaphases helps, because a small 45,X line is easily missed in a short count.
- Screen the associated organs: If the result is 45,X alone, an echocardiogram looks for bicuspid valve and coarctation, renal ultrasound checks for horseshoe kidney, thyroid function is measured and hearing is tested.
- Start growth hormone and oestrogen: Growth hormone is started in childhood to improve final height, and oestrogen is introduced around the expected age of puberty.
- Counsel early: Because ovarian failure is usually permanent, the family is counselled early about donor oocyte options.
Contrast this with a boy of tall stature with small testes and azoospermia, whose karyotype is usually 47,XXY; later management there turns to bone density, diabetes and cardiovascular risk rather than height.
Where the examiner separates the two
Four separators recur in examiner questions.
- Trap: treating the Barr body as the whole answer Correct: Turner has a single X and no Barr body, so a Barr-negative smear with primary amenorrhoea points to Turner, while a man with one Barr body and small testes points to Klinefelter.
- Trap: giving both syndromes the same cognitive profile Correct: Turner girls usually have normal intelligence with visuospatial and arithmetic weakness, whereas Klinefelter men more often have language and learning problems.
- Trap: swapping the associated lesions Correct: bicuspid valve and coarctation belong to Turner, while breast cancer and diabetes risk belong to Klinefelter.
- Trap: labelling azoospermia with normal testes as Klinefelter Correct: it should prompt karyotype and Y-microdeletion testing rather than a Klinefelter label alone.
Frequently asked questions
Which karyotype confirms Turner syndrome?
Turner syndrome is confirmed by peripheral blood karyotype, most often showing 45,X. Mosaic forms such as 45,X with 46,XX, and structural abnormalities such as isochromosome Xq, are also recognised and need the same clinical follow-up.
Why is Barr body testing useful in these syndromes?
Barr body testing counts inactivated X chromosomes in interphase nuclei. Turner syndrome is Barr-body negative because only one X is present, while Klinefelter syndrome shows one Barr body from its extra X, though a karyotype is still needed to confirm either diagnosis.
Which cardiac lesions must be screened for in Turner syndrome?
Every girl with Turner syndrome needs an echocardiogram at diagnosis to look for bicuspid aortic valve and coarctation of the aorta, the commonest cardiovascular associations. Aortic dilatation is also followed in adulthood, since aortic dissection risk is raised in Turner syndrome.
How does Klinefelter syndrome usually come to attention?
Klinefelter syndrome usually presents in adolescence or adulthood with infertility, small firm testes, gynaecomastia or delayed puberty, and sometimes learning difficulties. Many men are first diagnosed during evaluation of azoospermia, when raised FSH and low testosterone prompt a karyotype in Klinefelter syndrome.
Is growth hormone used in Turner syndrome?
Yes, growth hormone is used in Turner syndrome to improve adult height, usually started in childhood and continued until growth is complete. Oestrogen replacement is given later to induce and sustain puberty, because ovarian failure is permanent in most girls with Turner syndrome.