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Klinefelter syndrome :

Common chromosomal aberration in men with azoospermia.

Dr Sampurna Roy MD


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Klinefelter syndrome was first described in 1942 when Klinefelter et al.

They reported patients with gynecomastia, small testes, azoospermia (absence of sperm in the semen), and elevated gonadotropin levels.

In 1949, Barr and Bertram discovered a dense chromatin mass, later termed sex chromatin or Barr body, in the nerve cell nuclei of female but not male cats.

In 1956, 2 groups of investigators described patients with Klinefelter syndrome using results of buccal smears that demonstrated Barr bodies.

In 1959, the discovery that a patient with Klinefelter syndrome had 47 chromosomes, including an extra X chromosome (the karyotype of 47 XXY), established that the Barr body seen in Klinefelter syndrome  represents an additional X chromosome.

The presence of an extra X chromosome is considered the main etiologic factor of Klinefelter syndrome.

Klinefelter syndrome is the most common chromosomal aberration in men with azoospermia and affects approximately 1 in 500 male patients.

Klinefelter syndrome is associated with two or more X chromosomes and at least one Y chromosome.

The 'prototypic' man with Klinefelter syndrome has traditionally been described as tall, with narrow shoulders, broad hips, sparse body hair, gynecomastia, small testicles, androgen deficiency, azoospermia and decreased verbal intelligence.

47 XXY is most common (80% of cases), others are mosaics (Example: 46 XY / 47 XXY).


Pathology of Klinefelter Syndrome:

- Klinefelter syndrome is a leading cause of male infertility.

- Eunuchoid body habitus and failure of development male secondary sexual characteristics.

- Low testosterone lead to breast development (gynecomastia), feminine distribution of body fat, decreased libido, incomplete masculinization with female body hair distribution (sparse facial, armpit, and pubic hair).

- Atrophic testis and small penis. 

The decreased testosterone also causes an increase in two other hormones, follicle stimulating hormone (FSH) and luteinizing hormone (LH).

The increased amount of FSH and LH cause hyalinization and fibrosis, the growth of excess fibrous tissue, in the seminiferous tubules, where the sperm are normally located.

As a result, the testicles appear smaller and firmer than normal. Men with Klinefelter syndrome are infertile because they cannot make sperm.


Testicular atrophy

Testicular biopsies of prepubertal Klinefelter syndrome boys have shown preservation of seminiferous tubules with reduced numbers of germ cells, but Sertoli and Leydig cells have appeared normal.

The testes in the adult Klinefelter syndrome male are, however, characterized by extensive fibrosis and hyalinization of the seminiferous tubules, and hyperplasia of Leydig cells, but the tubules may show residual foci of spermatogenesis.


- Taurodontism may occur as one of many dentofacial manifestations of Klinefelter syndrome and can be detected before development of other physical characteristics.

Identification of patients with taurodontic teeth may lead to early recognition of Klinefelter syndrome and could substantially improve quality of life.


- Leg ulcers, especially in combination with hyperpigmentation, have been reported in association with Klinefelter syndrome.

- According to one study patients had severe varicose veins, which often appeared at an early age.

- Thromboembolic processes are also frequently observed.

The leg ulcers in patients with Klinefelter syndrome are usually attributed to venous insufficiency.

Patients had varicose veins, which were often severe and appeared at an early age.

- Plasma follicle-stimulating hormone and estrogen levels elevated, testosterone levels low.

- Breast carcinoma is at least 20 times more common in patients with Klinefelter syndrome.

Extragonadal germ cell tumors also occur with increased frequency in  Klinefelter syndrome.

- Androgen deficiency is an important risk factor for osteoporosis in men

- Diabetes mellitus is more common in patients with Klinefelter syndrome than in the general population.

- The increased incidence of autoimmune disorders, such as systemic lupus erythematous, rheumatoid arthritis, and Sjogren syndrome in patients with Klinefelter syndrome compared with other male subjects may be due to their lower testosterone and higher estrogen levels, since androgens may protect against, and estrogens promote, autoimmunity.

- Although patients with Klinefelter syndrome have above-average or superior intelligence poor school performance is common, with specific reductions in verbal IQ scores, delayed speech and language acquisition, diminished short-term memory, and decreased data retrieval skills.  

They may also have a higher incidence of dyslexia and attention-deficit disorder.

The constant features of Klinefelter syndrome are small testes and absent spermatogenesis, whereas the frequency of decreased facial and pubic hair, gynecomastia, and low testosterone levels varies.



Patients with Klinefelter syndrome should be treated with lifelong testosterone supplementation that begins at puberty, to secure proper masculine development of sexual characteristics, muscle bulk and bone structure, and to prevent the long-term deleterious consequences of hypogonadism.


Further reading:

Male hypogonadism: Klinefelter and Reifenstein syndrome. Birth Defects. 1975;1117- 22

Extragonadal germ cell tumors are often associated with Klinefelter syndrome.

Retroperitoneal extragonadal germ cell tumor in a patient with Klinefelter's syndrome.

Endodontic treatment in three taurodontic teeth associated with 48,XXXY Klinefelter syndrome: a review and case report.

Prepubertal diagnosis of Klinefelter syndrome in a patient with taurodontic teeth.

Klinefelter's syndrome as a model for skin changes in venous insufficiency.

Venous leg ulcers in a patient with Klinefelter's syndrome and increased activity of plasminogen activator inhibitor-1.

Testicular function in Klinefelter syndrome.

Rheumatic diseases and Klinefelter's syndrome.

Social behavior and autism traits in a sex chromosomal disorder: Klinefelter (47XXY) syndrome.

Immunohistochemical and quantitative study of interstitial and intratubular Leydig cells in normal men, cryptorchidism, and Klinefelter's syndrome.

Klinefelter syndrome in adolescence: onset of puberty is associated with accelerated germ cell depletion.

Establishment of testicular endocrine function impairment during childhood and puberty in boys with Klinefelter syndrome.


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Dr  Sampurna Roy  MD

Consultant Histopathologist (Kolkata - India)







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