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
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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