Turner Syndrome (TS) is a chromosomal condition affecting females, characterized by the complete absence of one X chromosome (monosomy X, 45,X). This genetic makeup affects development and leads to a range of physical features. Mosaic Turner Syndrome (MTS) is a variation where an individual has at least two different cell lines: one with the typical 45,X complement and another with a normal set of two X chromosomes (46,XX). The presence of the normal cell line introduces variability, raising the question of whether this variation leads to less severe symptoms compared to the classic form.
The Genetic Basis of Mosaicism
Mosaicism describes the presence of two or more distinct populations of cells, each with a different genetic makeup, originating from a single fertilized egg. This variation occurs after conception through an error in cell division, known as mitotic nondisjunction, during the early stages of fetal development. This error results in some cells retaining the normal 46,XX karyotype, while others become 45,X.
The resulting clinical picture depends heavily on the proportion of normal cells and their distribution within different tissues, especially those sensitive to X chromosome gene dosage. The normal 46,XX cell line acts as a genetic buffer, counteracting the effects of the monosomy X cells. A higher percentage of normal cells is associated with a significantly milder set of physical characteristics.
Comparing Severity: Features of Mosaic vs. Typical Turner Syndrome
The presence of the normal cell line in MTS often results in a milder phenotypic expression across several developmental and physiological systems.
Height and Ovarian Function
One of the most noticeable differences lies in adult height. Women with non-mosaic TS (45,X) are, on average, approximately 17 to 20 centimeters shorter than the general female population. Conversely, women with 45,X/46,XX mosaicism are reported to be only about 4 centimeters shorter on average, demonstrating a much smaller deviation from typical height.
Ovarian function and fertility also show a marked improvement in individuals with MTS. In typical TS, primary ovarian insufficiency is nearly universal, with spontaneous puberty occurring in a small minority, around 9% of cases. However, the likelihood of spontaneous breast development and the onset of menstrual periods is substantially higher in MTS, with some studies reporting rates of spontaneous menarche as high as 39%.
Organ-Specific Anomalies
The frequency and severity of organ-specific anomalies also tend to be reduced in the mosaic form, although risks are still present. Major congenital heart defects, such as coarctation of the aorta or a bicuspid aortic valve, occur in up to half of all TS cases. While screening for these conditions remains necessary for MTS, studies suggest that the frequency of both cardiac and renal anomalies is significantly lower in individuals who have a high percentage of 46,XX cells.
Health Monitoring and Long-Term Prognosis
Even with a milder presentation, individuals with Mosaic Turner Syndrome require consistent medical surveillance throughout their lives. Endocrine management frequently includes human growth hormone therapy, often started in childhood to maximize final adult height. For those who do not experience spontaneous pubertal changes, estrogen replacement therapy is initiated around the typical age of puberty to promote secondary sexual characteristics and support bone health.
Cardiovascular screening is particularly important, as the risk of aortic dilation and dissection persists, necessitating regular echocardiograms, often every five to ten years. Metabolic screening is also integrated into routine care due to an increased susceptibility to conditions like type 2 diabetes, hypertension, and hypothyroidism, especially Hashimoto’s thyroiditis.
The long-term prognosis for individuals with MTS is generally positive, especially with early diagnosis and consistent follow-up care provided by a multidisciplinary team. While life expectancy in the broader TS population is reduced compared to the general population due to cardiovascular complications, proactive management significantly mitigates these risks.