Turner's Syndrome: A Case Study
by: Carolyn Duda

Turner's Syndrome is a genetic disorder that affects about one in every 2000 females born. A female with a normal genetic make-up has two X-chromosomes in each of her cells, one which she received from her father and one which she received from her mother. On the other hand, the typical female with Turner's Syndrome has only one X-chromosome in each of her cells due to a nondisjunction event during meiosis of her parents' gametes. There are several variations on this theme as other similar chromosome anomalies occur in a smaller percentage of females with Turner's Syndrome.

The symptoms of Turner's Syndrome vary a great deal. The most pronounced characteristics of a Turner's patient are her short stature (less than five feet tall) and her failure to mature sexually. Other symptoms may include heart defects, kidney abnormalities, infertility, thyroid dysfunctions, a webbed neck, a low posterior hair line, a broad chest, a small mandible, and prominent ears (Nora and Fraser, 1989). Although mental retardation is found in about six percent of the patients with Turner's Syndrome, the majority of Turner's patients exhibit a normal mental capacity with only a small deficit in space-form perception and visual-motor skills (Nora and Fraser, 1989). In a recent study at Henry Ford Hospital in Detroit, 190 Turner's patients with different chromosomal abnormalities and symptoms were evaluated cytogenetically (Van Dyke et al., 1992). This paper will address the chromosome anomalies found in this study as it explains how these anomalies affect the patient with Turner's Syndrome.

Depending on the degree of nondisjunction of her parents' gametes, the genetic make-up of a Turner's patient can vary. As discussed above, the majority of patients have only one X-chromosome in all of their cells and thus they are karyotyped 45,XO. The cells in about 15 percent of Turner's patients contain a normal X chromosome plus an X-isochromosome. This isochromosome consists of the two long arms of the X-chromosome but no short distal arm. These individuals are karyotyped 46,XXp- (Nora and Fraser, 1989).

Lyon hypothesized that early in the development of a normal female embryo, random inactivation of one of the two X-chromosomes in each cell occurs. This allows the female to have the same amount of X-chromosome material as the average male has. Recent studies have shown that there are genes on the X-chromosome which escape this inactivation. While there are genes located in various regions of the X-chromosome which escape inactivation (Davies, 1991), many of these genes are located on the short distal arm (Brown and Willard, 1990). In this way, the normal female has functioning genes from one complete X-chromosome plus functioning genes from the still active short distal arm of the mostly inactivated X-chromosome. On the other hand, females with the X-chromosome without this short distal arm lack the genes which would normally have remained active. As a result, a female with this X-isochromosome displays the same phenotype as the typical Turner's female who has only one X-chromosome.

Another chromosome abnormality associated with Turner's Syndrome is due to a small X-derived ring as well as the normal X-chromosome in many of the cells of the body. This karyotype (45,XO / 46,Xr(X)) is further associated with mental retardation (Van Dyke et al., 1991). Experiments have been conducted which show that this X-derived ring lacks the X inactivation center in patients who display forms of mental retardation (Van Dyke et al., 1992). DNA probe technology can be used to determine if an X-derived ring lacks the inactivation locus. In a study done by Zenger-Hain, in situ hybridization with the X-centromere DNA probe DXZ1 was performed on previously G-banded slides, and the probe hybridized to the centromere regions of the normal X and the ring. Then a buccal smear was used to analyze for Barr bodies to determine the amount of activation versus inactivation. DAPI staining and FISH analysis with the X-centromer DNA probe DXZ1 was employed to distinguish the inactive X from the active X, and verified the presence of a sex chromatin mass in fibroblasts (Zenger-Hain et al., 1993). Using this technique and similar techniques, it can be determined if the X-derived ring is active or inactive.

Moreover, about 95% of Turner conceptions end as spontaneous abortions. The frequency of spontaneous abortions in patients with the X-derived rings would be expected to be higher than patients without the X-derived ring. Evidence for this lies in the fact that very few Turner's patients, and thus a very small percentage of the population, have this X-derived ring. In a recent study dealing with X-chromosome inactivation and its influence on the viability of both mice and humans, it was found that mice that are genotypically XO are more viable than humans because certain genes remain inactivated in the mouse. These same genes are activated in humans with the XO karyotype (Ashworth et al., 1991). If these genes are also activated in the X-derived ring, then this may explain why there are more spontaneous abortions with this karyotype. Further, the fetuses with the X-derived ring are more likely to survive to term if the ring is not in every cell.

In conclusion, Turner's Syndrome is a very complex genetic disorder that occurs in about one in every 2000 females. Besides the more common XO genotype, other genotypes exist which also show various symptoms of Turner's Syndrome. DNA probe technology can be used to identify various forms of the disease.


Ashworth, Alan and Rastan Sohaila, et al. X-Chromosome Inactivation may ... XO Humans and Mice. Nature: Vol. 351. May 30, 1991. Pp. 406-408.

Brown, C. J. and Willard, H. F. (1990). Localization of a Gene that Escapes....Short Arm: Implications for X Inactivation. American Journal of Human Genetics 46: 273-279.

Fraser, F. Clarke and Nora, J. James. Sex Chromosomes and the Mitochondrial Chromosome. Medical Genetics: Principles and Practice. Lea and Febiger. 3rd edition. 1989: 54-62.

Van Dyke, L. Daniel. And Wiktor, Anne, et al. Ullrich-Turner Syndrome With a Small Ring X Chromosome and Presence of Mental Retardation. American Journal of Medical Genetics 43: 996-1005. 1992.

Van Dyke, L. Daniel and Wiktor Anne , et al. Mental Retardation in Turner Syndrome. The Journal of Pediatrics. March 1991. 415-417.

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