2011 Group Project 3

From Embryology
Revision as of 22:12, 31 August 2011 by Z3289829 (talk | contribs)
Note - This page is an undergraduate science embryology student group project 2011.
2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip

Klinefelter's Syndrome


Klinefelter's syndrome is a condition wherein a male has an extra X chromosome. Typically, men and women have two sex chromosomes, women have two X chromosomes (46,XX), while men have an X and Y chromosome (46,XY). '46' refers to the total number of chromosomes present including both autosomes and sex chromosomes. However, men with Klinefelter's syndrome have three sex chromosomes (47,XXY) due to a process known as non-disjunction[1].

In some very rare cases there are two or more extra copies of the X chromosome present (48,XXXY, or 49,XXXXY). This generally results in more prominent clinical features. In approximately 20% of cases, 46,XY/47,XXY mosaicism can occur[2]. This refers to the situation where the extra chromosome is only present in some cells, this is due to errors occurring during mitosis.

Klinefelter's syndrome usually presents with a few standard clinical abnormalities. Affected men can have reduced fertility and hypogonadism. However, a high proportion of affected men may not show any symptoms and the severity of the disorder differs greatly from person to person. It is thought to be one of the most common conditions caused by non-disjunction[3].

This disorder was first described by Harry F. Klinefelter in 1942 [4]. He describes a disorder characterised by gynecomastia and a very specific type of hypogonadism, as well as an absence of spermatogenesis.


Klinefelter syndrome was first described by Harry F. Klinefelter and his colleagues in 1942. Their observations of nine patients where characterised by a number of peculiar symptoms; gynecomastia (breast development), azoospermia, hyalinised and small testes, absent spermatogenesis, elevated levels of follicle-stimulating hormone (FSH) and hypogonadism. [5] [6]

In 1949, Murray L. Barr and Ewart G. Bertram discovered that patients with Klinefelter’s syndrome had positive sex chromatin material in their epithelial cells, this is normal for females but not in males. [7] It was a dense chromatin mass which they later termed, Barr body. This discovery led to the use of smears of stained buccal mucosal cells which determined whether the infant’s genetic sex matched the phenotypic sex.

The late 1950’s led to a breakthrough in understanding Klinefelter’s syndrome. In 1956, investigations described 7 patients with Klinefelter’s syndrome as a result of the buccal smears that demonstrated Barr bodies (2). However, the cause of the syndrome remained unknown until 1959, when a discovery that a patient with KS had 47 chromosomes, including an extra X chromosome established that the Barr body seen in patients with KS corresponds to an extra X chromosome. [8]


The most common disorder of sex chromosomes in humans is 47, XXY mutations in around 1 in 500 males [9]. There are variations of the Klinefelter syndrome chromosomal aneuploidies, with a frequency of 1 in 50 000 male births. It is said that males born with this condition may go through life without being karyotyped [10]. Males born with Klinefelter syndrome tend to exhibit failure to produce sperm, and have low testosterone levels due to having very small testes. They have increased susceptibility to diabetes, cardiovascular disease and cancer. In about 80% of all cases, Klinefelter’s syndrome is in every cell of the body. As well, having a child with Klinefelter’s syndrome is not relevant to the age of the mother or father at the time of conception. Usually, the phenotype of Klinefelter’s syndrome only becomes evident after puberty. Prior to puberty however, the pituitary gland and gonad function is relatively normal in sufferers of the condition[11].Males with Klinefelter’s syndrome generally have IQs which are 10-15 points lower than the general population. There is also a higher chance that those affected will experience behavioural problems. The vast majority of males are not diagnosed prenatally with Klinefelter’s Syndrome. In Denmark in particular, only around a quarter of all people are diagnosed with Klinefelter’s Syndrome. A typical male suffering from Klinefelter’s is characterized by abnormally long legs and arm span, feminine distribution of adipose tissue including a condition known as gynecomastia, absent or decreased facial and pubic hair as well as small hyalinized testes and small penis [12].

Signs and Symptoms




Case Study


Androgen Therapy

Androgen therapy involves the replacement of testosterone. This is primarily given to stimulate the onset of puberty in affected males. Ideally, testosterone is given from the age that puberty usually occurs, in order to encourage normal development. In addition to this, it assists in treating or preventing some of the more typical clinical presentations of this disorder. Testosterone replacement encourages secondary sexual attributes, and helps ensure standard bone and muscle mass[13].

However, this has been associated with a decrease in fertility, especially if given early in life. Premature treatment has been suggested to result in delayed puberty and abnormal physical development during this period[14]. It is also recommended to stop testosterone replacement a few months prior to the administration of infertility treatment[15].


Aromatase inhibitors can be administered to men, in order to lower intratesticular estradiol levels. This is thought to encourage the production of testosterone and activate spermatogenesis[16]. There are two main methods used to treat non-obstructive azoospermia, microdissection testicular sperm extraction (TESE) and conventional TESE. These are methods of extracting what sperm is present in the testes for use in in vitro fertilisation (IVF). It has been shown that microdissection TESE has a higher rate of extraction, and allows for minial testicular damage[17], and so conventional TESE is slowly being replaced by microdissection TESE. The most common IVF technique used in these situations is intracytoplasmic sperm injection, where a single sperm is injected into a single oocyte. This means that for the highest chance of success, the extraction of both the sperm and the egg need to be well timed[18]. Before surgery, men are usually administered aromatase inhibitors for a few months. This is to restore the ratio of testoserone to esradiol back to normal levels, and to encourage the amount of viable sperm present[19][20]

Other Similar Defects

There are many similar genetic defects to Klinefelter Syndrome. Two main defects include, but are not limited to Turner Syndrome and 47, XYY Syndrome. In Turner Syndrome, there is either a small presence or complete absence of the X chromosome in girls, and this leads the girls to lack certain characteristics such as full grown ovaries, metabolic problems, short stature and decreased life expectancy [21]. The phenotype of Turner Syndrome is very variable, in the sense that girls can have the standard symptoms from it as aforementioned, or they can be asymptomatic and blend in with the rest of the population. In embryology, however, the embryo can have a web-like neck, low birth length and lymphedema of the dorsum of hands and feet. There can also be puberty delay because of gonadal dysgenesis. As well as all this, there can also be congenital defects of the heart, kidney and autoimmune system [22]. In terms of 47, XYY Syndrome, this is the only chromosomal aneuploidy which is not selected against before birth. The additional Y chromosome is from the father (paternal origin) and there is existing evidence that spermatocytes with additional Y chromosomes are selected against during gametogenesis[23]. A study was conducted into the prolonged P-R intervals of the PQR cycle of the heart. It was found that males with 47, XYY Syndrome had extremely prolonged P-R intervals and there was little other cardiac abnormalities detected, as seen in a male patient. More studies are currently being done to see if this phenomenon is just a coincidence or if it is a symptom of the syndrome[24].

Current Research

Neural systems for social cognition in Klinefelter syndrome (47,XXY): evidence from fMRI

  • Significance of additional X chromosome on neural systems



  1. <pubmed>17062147</pubmed>
  2. <pubmed>21397196</pubmed>
  3. <pubmed>17062147</pubmed>
  4. Klinefelter HF, Reifenstein EC & Albright F. Syndrome characterized by gynecomastia, aspermatogenesis without a-Leydigism, and increased excretion of follicle-stimulating hormone. American Journal of Clinical Dermatology 1942; 2: 615–627.
  5. <pubmed> 17415352 </pubmed>
  6. <pubmed> 21397196 </pubmed>
  7. <pubmed> 15729733</pubmed>
  8. <pubmed> 13632697</pubmed>
  9. <pubmed>17062147</pubmed>
  10. <pubmed>9160389</pubmed>
  11. <pubmed>21397196</pubmed>
  12. <pubmed>12574191</pubmed>
  13. <pubmed>20482304</pubmed>
  14. <pubmed>18832949</pubmed>
  15. <pubmed>18832949</pubmed>
  16. <pubmed>11792932</pubmed>
  17. <pubmed>21811543</pubmed>
  18. <pubmed>21716935</pubmed>
  19. <pubmed>11792932</pubmed>
  20. <pubmed>19616796</pubmed>
  21. <pubmed>21454226</pubmed>
  22. <pubmed>21271130</pubmed>
  23. <pubmed>10545600</pubmed>
  24. <pubmed>537021</pubmed>

2011 Projects: Turner Syndrome | DiGeorge Syndrome | Klinefelter's Syndrome | Huntington's Disease | Fragile X Syndrome | Tetralogy of Fallot | Angelman Syndrome | Friedreich's Ataxia | Williams-Beuren Syndrome | Duchenne Muscular Dystrolphy | Cleft Palate and Lip