Swyer Syndrome and Gonadal Dysgenesis
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Direct answer
Swyer syndrome is pure gonadal dysgenesis in a 46,XY individual, in which streak gonads fail to produce testosterone or anti-Müllerian hormone, producing a phenotypic female with a uterus and primary amenorrhoea. Because Y-chromosome material in a dysgenetic gonad carries a substantial risk of gonadoblastoma and germ cell malignancy, the streak gonads are removed once the diagnosis is made. Oestrogen replacement then induces puberty and protects bone.
What you must remember
- Genotype: a 46,XY karyotype with female phenotype, most often due to an SRY gene mutation or deletion on the short arm of the Y chromosome.
- Gonads: bilateral streak gonads without functional follicles, carrying a malignancy risk that is quoted widely, often as roughly 15 to 30 per cent where Y material is present.
- Müllerian structures: a uterus, fallopian tubes and upper vagina are present because the absence of anti-Müllerian hormone allows the ducts to develop.
- Presentation: primary amenorrhoea with absent breast development, infantile genitalia and often tall stature because epiphyseal fusion is delayed.
- Hormones: raised FSH and LH with low oestradiol confirm hypergonadotropic hypogonadism, and the karyotype must be checked for mosaicism.
- Turner distinction: Turner syndrome is 45,X with short stature and somatic features, whereas Swyer syndrome is 46,XY with a uterus and normal or tall stature.
A stepwise diagnosis in a girl with no puberty
A 16-year-old girl has female habitus, no breast development and no periods. Her ultrasound shows a small uterus and no clearly identifiable ovaries, and the karyotype returns 46,XY. The steps below set out the usual sequence from diagnosis to hormone replacement.
- Establish the karyotype: Confirm 46,XY and check for mosaicism, since a mosaic pattern changes the risk estimate and the family counselling.
- Measure gonadotrophins: Raised FSH and LH with low oestradiol confirm primary gonadal failure rather than a hypothalamic or pituitary cause.
- Look for the uterus: Pelvic ultrasound or MRI shows a uterus, which is the key clue that separates Swyer syndrome from complete androgen insensitivity.
- Remove the gonads: Bilateral gonadectomy is advised once the diagnosis is confirmed, with timing discussed at a specialist centre because of malignancy risk.
- Start oestrogen: Oestrogen replacement is begun around the usual age of puberty to induce breast and uterine development and to protect bone.
- Add progestogen: Once the uterus has been primed, cyclical progestogen is added to protect the endometrium, and donor-egg IVF can be considered for pregnancy.
Where the exam tries to catch you
The classic traps are confusing Swyer syndrome with Turner syndrome and leaving streak gonads in place.
- Trap: Diagnose Swyer syndrome as Turner syndrome because of primary amenorrhoea. Correct: Turner syndrome is 45,X with short stature and somatic features, whereas Swyer syndrome is 46,XY with a uterus.
- Trap: Leave the streak gonads in place to see whether they function. Correct: Streak gonads produce no useful hormones and carry gonadoblastoma risk, so gonadectomy is advised once the diagnosis is confirmed.
- Trap: Assume any 46,XY girl with primary amenorrhoea has androgen insensitivity. Correct: Complete androgen insensitivity has normal breast development and no uterus, whereas Swyer syndrome has absent breast development and a uterus.
- Trap: Start oestrogen alone after gonadectomy in a woman with a uterus. Correct: Cyclical progestogen is needed once oestrogen is given, to protect the endometrium from hyperplasia.
Frequently asked questions
What distinguishes Swyer syndrome from Turner syndrome?
Swyer syndrome is 46,XY with a uterus and streak gonads, while Turner syndrome is 45,X with short stature and somatic features. The uterus on imaging and the karyotype together separate Swyer syndrome from Turner syndrome.
Why are the gonads removed in Swyer syndrome?
The streak gonads in Swyer syndrome have no useful function and carry a risk of gonadoblastoma and germ cell tumours, particularly where Y-chromosome material is present. Gonadectomy removes this malignancy risk, and hormone replacement then supplies the missing sex steroids.
Why does a woman with Swyer syndrome have a uterus?
A uterus develops in Swyer syndrome because the streak gonads do not secrete anti-Müllerian hormone, so the Müllerian ducts persist. This uterus is a key imaging clue that distinguishes Swyer syndrome from complete androgen insensitivity.
What hormonal pattern supports the diagnosis of Swyer syndrome?
Raised FSH and LH with low oestradiol point to primary gonadal failure in Swyer syndrome. The diagnosis is confirmed by a 46,XY karyotype, which must also be checked for mosaicism.
When is oestrogen started in Swyer syndrome?
Oestrogen replacement is started around the usual age of puberty in Swyer syndrome to induce breast development and maintain bone health. A progestogen is added later once the uterus has been primed, to protect the endometrium.