Klinefelter Syndrome

Klinefelter syndrome is due to an extra copy of an X chromosome in males (47,XXY).  Adult males have hypergonadotrophic hypo-gonadism and are invariably infertile.  However, lifespan is normal and many males may never be diagnosed.

Epidemiology

• Prevalence is ~1/600–1/800 male births
• There is a significant maternal age effect with 1/300 at maternal age 43 years

Clinical presentation

• 47,XXY may present antenatally following chorionic villous sampling (CVS) or amniocentesis
• Babies appear normal
• Increased incidence of undescended testes
• Delayed puberty
• Gynaecomastia
• Infertility

Physical signs

• Males tend to have a taller final height (186cm 47,XXY vs. 176cm 46,XY)
• Gynaecomastia
• Increased carrying angle
• Centripetal obesity
• Hypogonadism
• Normal intelligence

Complications

• IQ: usually only lower by 10-15 points compared to siblings. Overall intelligence is normal as an adult although ~60% will need some degree of additional educational help.  The majority of patients tend to be passive and good natured
• Cancer risk: there is no good evidence for a general increased risk of cancer although there is a 3% risk increase in breast cancer.  There is a <1% risk of primary germ cell tumour
• In adult life there is an increased risk of diabetes and cardio-vascular disease
• Hypogonadism: delayed puberty, gynaecomastia, infertility
• Osteoporosis