Genetically, TS is due to the absence of all or part of one sex chromosome, usually one X. This abnormality, also called monosomy X, is denoted medically as the 45,X (older literature used XO) karyotype, as opposed to the usual 46,XX female karyotype. Many, perhaps most, girls and women with TS are actually mosaic, meaning that they have cells with more than one karyotype. Often there is a mix of 46,XX and 45,X cells, and in this case the resulting clinical abnormalities tend to be milder than in 45,X TS. Mosaicism, especially 45,X/46,XX, is frequently detected by prenatal diagnosis (amnicentesis). Occasionally there is mosaicism for cells containing Y chromosome material - but not enough to cause male sexual features.
Girls with TS and Y chromosome mosaicism are at increased risk of developing a tumor of the gonads and should have their non-functioning ovaries removed.
Molecularly, most TS features result from having one rather than two copies of certain X chromosome genes. To date, one gene called SHOX has been clearly implicated in TS. Loss of one copy of SHOX is the main cause of short stature in TS. Identification of TS genes may lead to better treatments for short stature and other symptoms.
How is Turner syndrome diagnosed?
Diagnosis is made through a test called a karyotype, which is usually performed on cells in the amniotic fluid before birth and on cells in the blood after birth. A trained specialist counts the chromosomes in the white blood cells and looks for abnormalities. Females normally have two X chromosomes (46,XX) and males have one X and one Y (46,XY). Turner syndrome individuals are missing all or part of one of their sex chromosomes. About half of girls with Turner syndrome have only one X chromosome (45,X). Another third have two X chromosomes, but part of one X is missing. Other individuals with Turner syndrome have a mosaic pattern: some of their cells are missing an X chromosome (45,X), while other cells have different chromosome composition (such as 46,XX) Turner syndrome may be diagnosed throughout the life span, including adulthood, if signs are subtle.
Signs that indicate a karyotype is needed can include:
- Fetal abnormalities such as cystic hygroma (fluid around the neck), or incidentally when a routine amniocentesis is performed (e.g., for advanced maternal age)
- Webbed neck (excess skin) or lymphedema (swelling of hands and feet) in newborns
- Specific heart problems in infants
- Slow growth and/or short stature
- Delayed puberty or amenorrhea (lack of menstrual cycles)
- Infertility or menstrual irregularities
How reliable are the FISH and the Karyotype tests?
It's important to understand that even though the classic TS karyotype is 45,X (completely missing the second X chromosome in all cells studied, like me), there are a number of variations. Mosaicism is one of these variations, and it means that they saw cells with at least two different chromosome configurations. The fact that your daughter's starts with 46,X just means that they saw at least one cell line that had 46 chromosomes. From that point the karyotype report probably gets even more confusing, as it gets into a lot of shorthand that the labs use to communicate what they see.
FISH and karyotype are studies done very routinely at a lot of different labs, in a standardized way. The combination of the two tests confirm each other. A geneticist or genetic counselor can help interpret your daughter's specific results for you.