Klinefelter’s Syndrome

Please see this 30 year old man with concerns about breast swelling. He is having difficulty conceiving with his wife.

HISTORY (3mins)

  • Fertility history
    • How long have they been trying
    • Any previous children
    • Frequency of intercourse
    • Erection difficulties
    • Sex drive
    • Ejaculation
    • Any blood in sperm
  • PMH of:
    • Mumps/testicular infection, STIs
    • Chemo/Radiotherapy
    • Trauma
    • Torsion
    • Failure of testicular descent
    • Surgery- hernia/testis/prostate
    • Liver/kidney/cancer
  • Dx including those that cause gynaecomastia e.g. digoxin, spironolactone
  • Fx
  • Sx: occupation, smoking, alcohol, illicit drugs
  • Klinefelter’s history:
    • Breast size: onset and duration of breast enlargement, tenderness
    • Facial and body hair
    • Sexual dev and height
    • Voice
    • Muscle bulk
    • How did they do at school, any evidence of learning difficulties
    • Complications: SOB, cough, CP
  • Kallmans
    • Sense of smell (anosmia/hyposmia)
  • Haemochromatosis
    • Joint pains, diabetes, tanned
  • Prolactinoma
    • Headache, vision, nipple leak


EXAMINE ( 3mins)

  • Stand to assess height
  • Gynaecomastia- palpate. Check for signs of liver disease.
  • Check armpit hair, face hair, muscle bulk
  • Offer to examine external genitalia and inguinal LNs
  • CVS murmur: Mitral valve prolapse

ICE and EXPLANATION (2 mins)

For example:

“This is not my area of expertise but I think we should start by doing some basic tests such as checking your semen to see the quality of your sperm and checking your levels of testosterone.  I’ll refer you both to a fertility clinic and to a hormone doctor. It may be that you have a condition called klinefelter’s syndrome- this is a condition where you have an additional X chromosome. If so you may need testosterone injections to improve the symptoms. Unfortunately these don’t help fertility but there are other options to help you conceive”



Klinefelter’s syndrome is the most common congenital abnormality causing primary hypogonadism, occurring in approximately 1 in 1000 live male births.

The syndrome is the clinical manifestation of a male who has an extra X chromosome. The most common genotype is 47 XXY.

The condition was first described in 1942 by Dr Harry Klinefelter Jnr . He described a series of men who:

  • Were tall (around six feet).
  • Had small testes or hypogonadism.
  • Were unable to produce sperm.
  • Had sparse facial and body hair.
  • Had gynaecomastia.

Klinefelter’s syndrome often goes undiagnosed in affected males until they are adults

Adults may present with hypogonadism or subfertility. There may also be failure of sexual maturation.  Although the majority have normal intelligence, they may also tend to have minor developmental and learning disabilities, or some degree of difficulty with language throughout their lives.

The clinical features vary and many individuals may have only subtle clinical features.

There is a predisposition to develop morbidities later in life including pulmonary diseases such as chronic bronchitis, bronchiectasis, and emphysema ; cancers, including germ cell tumours (particularly extragonadal tumours involving the mediastinum) , breast cancer, and possibly non-Hodgkin lymphoma ; varicose veins, leading to leg ulcers ; systemic lupus erythematosus, probably due to the extra X chromosome ; and diabetes mellitus  and other endocrine disorders. There is increased risk of cardiovascular disease, mitral valve prolapse and osteoporosis.




Diagnosis of Klinefelter’s syndrome usually can be made by chromosomal analysis to determine the karyotype

Elevated serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) concentrations (FSH>LH) and low serum testosterone concentration

BP, BMI, glucose, cholesterol, hep B, C, HIV, U+E, chlamydia, gonorrhoea

Semen analysis: vol, number, concentration, motility, vitality, morphology

Echo (Mitral valve prolapse)

Dexa (Osteoporosis)



Multidisciplinary team follow-up is required to monitor for long-term problems. The team may need to include an endocrinologist, geneticist (genetic counselling), psychologist, physiotherapist, speech therapist and fertility specialist. There are support groups available.

Testosterone deficiency and the resulting hypogonadism, if present, can be treated with testosterone injections. This increases muscle bulk, facial and body hair, libido, testes, bone strength but has  no effect on fertility.  Testosterone injections may reduce the risk of most of the long-term complications associated with Klinefelter’s syndrome.

With regards to Fertility treatment, intracytoplasmic injection of sperm and artificial insemination by donor are options

Surgery may be required for gynaecomastia


Differential Diagnoses:

Male hypogonadism:

  • Testes
    1. Congenital
      1. Klinefelter’s, cryptorchidism, autoimmune against testes, anorchia, noonans, myotonic dystrophy
    2. Acquired
      1. Orchitis, trauma, drugs eg. Spiro, ketoconazole, cimetidine, alcohol, marijuana, digoxin, cytotoxics, RT, torsion
    3. Systemic
      1. Liver disease, kidney disease, infiltration, vascular, cancer
    4. Pit/Hypothalamus
      1. Congenital
        1. Kallmans, haemochromatosis, prader willi, LH deficiency
      2. Acquired
        1. Hypopit, prolactinoma, high oestrogen
      3. Systemic
        1. Cushings, anorexia nervosa, obesity


Written by Sarah Kennedy


Resources used include those listed in the references section of this webpage and also: