45,X/46,XY mosaicism

Although similar in some ways to true hermaphroditism, the conditions can be distinguished histologically and by karyotyping.[5] The observable characteristics (phenotype) of this condition are highly variable, ranging from gonadal dysgenesis in males, to Turner-like females and phenotypically normal males.[6] The phenotypical expression may be ambiguous, male or female depending on the extent of the mosaicism. The most common presentation of 45,X/46,XY karyotype is phenotypically normal male, next being genital ambiguity.[7]

There is a range of chromosomal anomalies within 45,X/46,XY where the variations are very complex, and the actual result in living individuals is often not a simple picture.[1] Most patients with this karyotype are known to have abnormal gonadal histology and heights considerably below their genetic potential. High gonadotropin levels have been described in both male and female patients, as well as low levels of testosterone in male patients. Dosage loss of SHOX gene is commonly associated with short stature.[8] Psychomotor development is normal.

As the gonads may not be symmetrical, the development of the Müllerian duct and Wolffian duct may be asymmetrical, too.[9] Because of the presence of dysgenetic gonadal tissue and Y chromosome material, there is a high risk of the development of a gonadoblastoma.[1]

In a normal situation, all the cells in an individual will have 46 chromosomes with one being an X and one a Y or with two Xs. However, sometimes during this complicated early copying process (DNA replication and cell division), one chromosome can be lost. In 45,X/46,XY, most or all of the Y chromosome is lost in one of the newly created cells. All the cells then made from this cell will lack the Y chromosome. All the cells created from the cells that have not lost the Y chromosome will be XY.[10] The 46,XY cells will continue to multiply at the same time as the 45,X cells multiply. The embryo, then the fetus and then the baby will have what is called a 45,X/46,XY constitution. This is called a mosaic karyotype because, like tiles in mosaic floors or walls, there is more than one type of cell.

There are many chromosomal variations that cause the 45,X/46,XY karyotype, including malformation (isodicentricism) of the Y chromosomes, deletions of Y chromosome or translocations of Y chromosome segments.[2] These rearrangements of the Y chromosome can lead to partial expression of the SRY gene which may lead to abnormal genitals and testosterone levels.

Identification of 45,X/46,XY karyotype has significant clinical implications due to known effects on growth, hormonal balance, gonadal development and histology.[2] 45,X/46,XY is diagnosed by examining the chromosomes in a blood sample.

The age of diagnosis varies depending on manifestations of disease prompting reason for cytogenetic testing. Many patients are diagnosed prenatally due to fetal factors (increased nuchal fold, or abnormal levels of serum), maternal age or abnormal ultrasounds, while others will be diagnosed postnatal due to external genital malformation.[2] It is not uncommon for patients to be diagnosed later in life due to short stature or delayed puberty, or a combination of both.[7]

45,X/46,XY mosaicism can be detected prenatally through amniocentesis however, it was determined that the proportion of 45,X cells in the amniotic fluid cannot predict any phenotypic outcomes, often making prenatal genetic counselling difficult.[6]

• Gonadal dysgenesis
• Mosaic (genetics)
• Turner syndrome