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There are two significant genetic syndromes that can affect male fertility, which are:

    1. Klinefelter Syndrome
    2. Congenital Adrenal Hyperplasia

Klinefelter Syndrome

Klinefelter syndrome is a male-only genetic condition caused by an extra ‘X’ sex chromosome. It’s present in about 1 in 500-1,000 newborn boys. While it’s not an inherited condition, women over 35 are slightly more likely to have boys with this syndrome than younger mothers.

All of our genetic material is DNA sequences held on 46 chromosomes, and these are identical between the sexes except for the ‘X’ or ‘Y’ chromosomes, which determine our sex:

  • Two X chromosomes are normal for females
  • One X and one Y chromosome are normal for males
  • In Klinefelter syndrome, the boys and men have ‘XXY’ have three sex chromosomes; two X and one

Many boys with Klinefelter syndrome show no symptoms or some of the possible symptoms after puberty. There is significant variation in symptomology, but the condition makes all Klinefelter syndrome men infertile without specialist help.


  • Boys with abnormal body proportions: tall with long legs, short trunk, broad hips
  • Muscle weakness, weaker bones, and a lower energy level than other boys i
  • Abnormally large breasts and small, firm testes
  • Infertility
  • A lack of interest in sex, or sexual problems
  • Little pubic, armpit or facial hair


Infertility is why men usually get tested for Klinefelter syndrome after semen samples show a lack of sperm. Blood hormonal tests will show:

  • Raised levels of estradiol (one of the estrogens)
  • High follicle-stimulating hormone (FSH) levels
  • High luteinizing hormone (LH) levels
  • Low testosterone levels

The definitive test is a chromosome (karyotype) test that shows the extra X chromosome.


The genetic variation that causes the condition is irreversible. However, testosterone treatment is an option for men wanting a more masculine appearance and identity, and it will increase body hair, energy and sex drive and improve mood and concentration.

As far as fertility is concerned, Klinefelter men cannot have children without specialist sperm-retrieval techniques. These have made it possible for men with Klinefelter syndrome to father a child, and by 2010 over 100 successful pregnancies following IVF that used surgically-recovered sperm material from men with Klinefelter syndrome. ii

Congenital Adrenal Hyperplasia

Congenital adrenal hyperplasia is an inherited disorder of the adrenal glands that affects about 1 in 10,000 to 18,000 newborn babies. It can affect both sexes, but it affects female fertility more than men.

The critical issue is the lack of an enzyme the adrenal gland needs to make the hormones cortisol and aldosterone. The lack of cortisol and aldosterone makes the body produce more androgens (male sex hormones) to compensate, which causes male characteristics to appear early (or inappropriately) in life.


Boys won’t have any apparent problems at birth; however, they may appear to enter puberty as early as 2-3 years of age and then develop:

  • A deep voice
  • The early appearance of pubic and armpit hair and the early development of male characteristics
  • An enlarged penis and small testes
  • Well-developed muscles

Girls will usually have normal female reproductive organs (ovaries, uterus and fallopian tubes), but they may also experience:

  • Abnormal menstrual periods or a failure to menstruate
  • A deep voice
  • The early appearance of pubic and armpit hair, and generally excessive hair growth
  • Genitals that look ambiguous and can appear more male than female

Both boys and girls will be tall as children, but as adults will be much shorter than average.


  • Blood tests show high levels of 17-OH progesterone and DHEA sulphate and low levels of aldosterone and cortisol, which indicates congenital adrenal hyperplasia and abnormal salt levels usually accompany this
  • Other indicators are urine tests that show abnormal salt levels, plus high levels of urinary 17-ketosteroids and low or normal levels of 17-hydroxycorticosteroids
  • X-rays will reveal bones that appear older than usual for that age


Treatment aims to return hormone levels to normal by taking a form of cortisol (dexamethasone, fludrocortisone, or hydrocortisone) daily. Times of stress, severe illness or surgery often require extra medication.

Support groups

National Adrenal Diseases Foundation:www.medhelp.org/nadf/
The MAGIC Foundation:www.magicfoundation.org
The CARES Foundation:www.caresfoundation.org

i http://www.nichd.nih.gov/health/topics/klinefelter_syndrome.cfm
ii “Should non-mosaic Klinefelter syndrome men be labelled as infertile in 2009?”. Fullerton G, Hamilton M, Maheshwari A. (2010). Hum Reprod. 2010 Mar;25(3):588–97.