Paper I
Question
Klienfilter syndrome
Answer
Klinefelter syndrome is a disorder of male sexual development resulting from the presence of one or more extra X chromosomes.
Karyotype
- Classic karyotype: 47,XXY (most common); variants include 48,XXXY, mosaic forms (46,XY/47,XXY)
Pathogenesis
- Results from non-disjunction of sex chromosomes during meiosis in either parent, producing a gamete with an extra X chromosome
- The extra X chromosome causes dysgenesis of the seminiferous tubules, with progressive hyalinization and fibrosis, while Leydig cells are relatively preserved (though their function is often impaired)
Clinical features
- Testicular atrophy — small, firm testes
- Infertility (most common cause of male infertility due to a chromosomal abnormality) — due to azoospermia/severe oligospermia
- Reduced testosterone with elevated LH/FSH (hypergonadotropic hypogonadism)
- Eunuchoid body habitus — tall stature with disproportionately long extremities
- Gynaecomastia
- Reduced facial/body hair, female pattern pubic hair distribution
- Mild intellectual impairment in some cases
- Increased risk of extragonadal germ cell tumours and breast cancer (relative to other males)
Laboratory diagnosis
- Karyotyping — demonstrates 47,XXY
- Buccal smear — demonstrates presence of Barr body (normally absent in males, present when ≥2 X chromosomes are present)
- Hormonal profile — low testosterone, elevated LH and FSH