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Klinefelter syndrome

  • Klinefelter syndrome, also known as 47, XXY is an aneuploidy which affects 1 in 1,000 males.
  • Apart from occasional exceptions, males with Klinefelter syndrome are infertile, and usually have accompanying underdevelopment of some of their secondary sexual characteristics.

Clinical features

  • Infertility is usual in males with Klinefelter syndrome.
  • The testicles do not enlarge fully during puberty, and are small in adults, who thereby manifest hypogonadism. Secondary sexual characteristics such as pubic, armpit and facial hair may be underdeveloped.
  • Enlarged breasts (gynaecomastia) may feature.
  • Male individuals may have above-average height, but relatively longer limbs and a shortened trunk.
  • Osteoporosis may occur.
  • Life span is unaffected.
  • There can be a tendency to passiveness in behaviour, and the average IQ measurement falls 10-15 points below the mean for their siblings. The proportion of boys with Klinefelter syndrome who receive additional educational support is raised.

Diagnosis

  • Diagnosis is usually made in adulthood, during the investigation of infertility. Some individuals are diagnosed prenatally from fetal karyotype taken in the context of raised maternal age. The majority of individuals go undiagnosed.
  • The diagnosis may be suspected from the clinical features, which may be noted incidentally at routine consultation for an unrelated issue.

Genetic basis

  • Defined as an aneuploidy (numerical chromosomal anomaly), the presence of an additional X chromosome brings the total number of chromosomes in cells up to 47.
  • The extra X chromosome arises for the first time at meiosis in the gonad of one of the parents, or, in mosaic cases, at an early mitotic division of the fertilised egg. The recurrence risk is low, being less than 1%. Parents of boys with Klinefelter syndrome are not routinely karyotyped.

Clinical management

  • Testosterone replacement therapy from early adolescence may assist the development of secondary sexual characteristics and may also help to prevent osteoporosis.
  • Sperm retrieval (which typically requires testicular biopsy) and intracytoplasmic sperm injection (ICSI) has enabled occasional men with Klinefelter syndrome to father children.

Genetic testing

  • The presence of an additional X chromosome may be an unexpected prenatal discovery during chorionic villus sampling.
  • Karyotyping may be used to visualise the presence of the extra chromosome.
  • The additional X chromosome can also be detected on buccal (cheek) cells using fluorescent hybridisation (FISH), or on DNA by qfPCR (quantitative fluorescent polymerase chain reaction) or microarray CGH (comparative genomic hybridisation) techniques.

 

This information is intended for educational use and was current in August 2013. For clinical management, it is recommended that local guidelines and protocols are used.