Genetic Features of Turner Syndrome
Humans normally have a total of 46 chromosomes (which are tiny, DNA-containing elements) that are present in every cell of the body. DNA encodes genes, which specify all the proteins that make up the body and control its functions.
In humans, there are 23 matched pairs of chromosomes in every cell. Each cell contains 22 pairs of chromosomes called autosomes that are the same in males and females. The remaining pair of chromosomes, the X- and Y-chromosomes, are not shaped similarly, and thus are not matched in the same way as the autosomes.
The X- and Y-chromosomes are called sex chromosomes. They are responsible for the difference in development between males and females. A Y-chromosome contains genes responsible for testis development; and the presence of a X-chromosome paired with a Y-chromosome will determine male development. On the other hand, two X-chromosomes are required for normal ovarian development in females.
During the process in which oocytes (eggs) or sperm are formed, one of the sex chromosomes is sometimes "lost" (see Figure 1). An embryo receiving only a Y-chromosome can not survive, but an embryo receiving only a X-chromosome may survive and develop as a female with Turner syndrome.
In order to examine the matching pairs of chromosomes for a person, doctors can perform a blood test and look at the chromosomes found in the lymphocytes, a particular type of blood cell. This will determine the karyotype of that individual.
The karyotypeof X-monosomy is termed, "45X" meaning that an individual has 44 autosomes and a single X-chromosome. The usual female karyotype is 46, XX.
A sex chromosome may also be lost during early stages of embryonic development, such that some cells of the growing body receive a single X chromosome (see Figure 2). This condition is called mosaicism, and the clinical features of Turner syndrome correlate with the relative percentage of 45X cells within the body.
If only a small percentage of cells have been affected, the phenotypes of Turner syndrome may be relatively mild. In other words, mosaicism may lessen the severity of certain clinical features. An example of the lessened effects due to mosaicism is if a woman with Turner syndrome experiences regular menstrual cycles until her late 20's rather than not having any menstrual cycle at all (see Puberty/Reproduction section, Clinical Features).
The genetic diagnosis in such cases may require the examination of many, many blood cells, and/or the examination of other cell types such as skin cells. The genotype is usually specified as 45X (10)/46XX (90) to indicate for example, that 10% of cells examined were found to have X-monosomy.
A third cause of Turner syndrome involves X-chromosome defects rather than complete loss. For example, one X-chromosome may be fragmented, have portions deleted or other structural problems such as ring formation preventing the normal expression of X-chromosome genes.
The clinical consequences of having one normal and one structurally defective X-chromosome vary widely (See Figure 3). A small deletion may result in a single feature such as ovarian failure or short stature and no other effects. Larger deletions or deletions affecting critical areas regulating the whole chromosome may result in a full spectrum of Turner syndrome problems. Abnormal X chromosomes are frequently lost during cell division during embryogenesis, resulting in an individual that is mosaic for 46,X,abnX and 45,X cell lines (see Figure 4).
Moreover, the presence of small ring X-chromosome causes severe consequences, because in addition to absence of some important genes, there may be deleterious expression of X-chromosome genes that are normally silenced, or inactivated in the second X-chromosome. The diagnosis of abnormal X-chromosomes may require specialized, molecular cytogenetic studies to identify small deletions or inversions of X-chromosome material.
While Turner syndrome is genetic in that it involves the loss or abnormal expression of X-chromosome genes, it is not usually hereditary in the conventional sense. That is, it does not typically "run in families." The one exception to this observation are families with a X-chromosome deletion which is stable enough to be passed down through the generations and which also allows fertility.
Turner syndrome affects all races, nationalities and regions of the world equally, and parents who have produced many unaffected children may still have a child with Turner syndrome. There are no known toxins or environmental hazards that increase the chances of Turner syndrome.
A woman with Turner syndrome has a low probability of being fertile, since the ovaries are negatively impacted in this disorder. However, if she does become pregnant and passes on her normal X-chromosome to her offspring, no continuation of the syndrome is expected.