Klinefelter
- Usually one extra X chromosome – 47 XXY
- 1 in 500 to 1 in 1000
- Most common sex chromosomal abnormality
- Variable phenotype – may appear normally virilised
- Medically unassisted paternity very rare
- 95 % of cases have small testes, azoospermia and elevated GnRH
- Other associated include learning difficulties, tall height, are not as common
- Increased incidence of mediastinal germ cell tumours
- Of men with Klinefelter:
- 8 % have sperm in the ejaculate
- Approx half will have sufficient mature sperm in testis for retrieval and IVF/ICSI
- Also associated with lower testosterone levels – this may be identified after puberty and subsequent testosterone replacement may be troublesome for fertility outcomes
Y chromosome microdeletions
- Testing indicated if sperm count < 5 / million or azoospermia
- Area on long arm of Y chromosome – azoospermia factor (AZf) – found to be crucial for sperm production
- AZFc mutations may still have some spermatogenic potential
- AZFa and AZFb mutations -> extremely unlikely to have any success with harvesting
- These genes may be passed on to any sons
Cystic fibrosis transmembrane conductance regulator (CFTR)
- Nearly all men with cystic fibrosis have congenital bilateral absence of the vasa
- Bilaterally absent vasa is a phenotype of a spectrum of CFTR mutations
- 2/3 of men with congenitally bilaterally absent vasa have CFTR mutations
- More than 1600 mutations if CFTR identified
- Approx 1 in 20 people may be carriers for CFTR mutations – therefore in a man with bilaterally absent vasa, both male and female partners should be tested
- Men may have minimal or relatively clinically insignificant stigmata of CF
- Spermatogenesis in men with congenitally absent vasa/CFTR mutations is typically normal
- Need sperm retrieval and ICSI
Kallmann syndrome
Classic Kallmann syndrome is X-linked recessive disorder associated with anosmia