Klinefelter syndrome

Disease class: Hypogonadism

Disease class: Sex chromosome disorders of sex development 

Karyotype

47 XXY

Pathophysiology

1. There is a nondisjunction event during paternal or maternal meiosis I (gametogenesis).
2. A 24th chromosome (either X or Y) is retained in the gamete.
3. During contraception, the gametes fuse to form a zygote with (23+24) 47 chromosomes instead of the normal 46 chromosomes. The karyotype is 47 XXY.
4. The zygote begins mitosis to become a morula. All the cells have the 47 XXY karyotype. 
5. A foetus develops with Klinefelter syndrome and survives birth.
6. The neonate with Klinefelter syndrome has decreased testicular endocrine function (primary hypogonadism). There is often a low serum testosterone level, but high serum follicle-stimulating hormone and luteinizing hormone levels.
7. The patient lives with primary hypogonadism and they are incapable of sperm development (azoospermia).

 

Symptoms

• Infertility
• Gynaecomastia 

Signs

• Height: taller than average
• Reduced body hair growth
• Reduced muscle growth and strength
• Reduced development of secondary sex characteristics
• Microorchidism (abnormally small testes)
• IQ is in the normal range (but often a small but significant degree lower than average)
• Reduced muscle control and coordination relative to developmental age
• Speech and language impairment relative to developmental age