Biology of DSDs: Turner Syndrome

Description

Turner syndrome is a sex chromosome condition in females where only one X chromosome is present and the other X chromosome is missing or altered. The missing or altered X chromosome affects development before and after birth, most often leaving affected females with a loss of ovarian function and mild to serious physical differences.

If you want to help improve medical research and psychological support for individuals with these conditions, you can donate to DSDFamilies (https://dsdfamilies.org/donate).

Sources

[1] NIH. (2020). Turner Syndrome. Genetics Home Reference, National Library of Medicine.

[2] Danielsson, K. (2020). Turner syndrome (monosomy X) and pregnancy loss. Verywellfamily.

[3] LOCAH. (2018). The intersex masterpost. Medium.

[4] Witchel, S. (2018). Disorders of sex development. Best Practice and Research in Clinical Obstetrics and Gynecology, 48, 3.

[5] TSF. (2019). Diagnosing Turner Syndrome. Turner Syndrome Foundation.

[6] Mayo Clinic. (2020). Turner Syndrome Diagnosis and Treatment. MayoClinic.org.

[7] Bondy, C. (2007). Care of Girls and Women with Turner Syndrome. Journal of Clinical Endocrinology & Metabolism, 92(1), 10-25.

[8] Fuchs, M., et al. (2019). Long‐Term Outcomes in Patients With Turner Syndrome A 68‐Year Follow‐Up. Journal of the American Heart Association, 8(11).

For more information about Turner syndrome and various support groups:

[1] Turner Syndrome Foundation (https://dsdfamilies.org/charity)

[2] Turner Syndrome Global Alliance (https://www.tsgalliance.org)

[3] Turner Syndrome Society of the United States (https://www.turnersyndrome.org)

Transcript

Turner syndrome is a sex chromosome condition in females where only one X chromosome is present and the other X chromosome is missing or altered. Half of all individuals with Turner's have a karyotype of 45,X (known as monosomy X), instead of the typical 46,XX, and the other half have X chromosome mosaicism, where some cells in the body are 45,X and others are 46,XX. The missing or altered X chromosome affects development before and after birth, most often leaving affected females with a loss of ovarian function and mild to serious physical differences. Turner syndrome is one of the more common DSDs, affecting about 1 in 2500 newborn girls--a rate of around 0.04% of births.

At conception, the chromosome set for Turner's begins with 45,X. Like Klinefelter's, an error during cell division called nondisjunction results in an atypical distribution of chromosomes in sperm or egg cells. During typical reproductive cell division, each egg gets a single X chromosome (leaving four egg cells each with an X), and each sperm gets either an X chromosome or a Y chromosome. With Turner syndrome, a sperm or egg cell may be missing the necessary X chromosome at conception, or the second X chromosome may be defective. If either of these cases occurs, the child will develop with only one active X chromosome in each cell. Research has shown that 1-2% of all conceptions have the karyotype of 45,X, but 99% of those affected babies are miscarried or stillborn.

Furthermore, there is no Y equivalent to Turner syndrome, where a fetus would develop with only a Y chromosome. At least one X chromosome is required for all fetuses to survive.

Around the 8th week after conception, the 45,X fetus undergoes gonadal differentiation. In the absence of SRY, transcription factors FOXL2, WNT4, and RSPO1 initiate and maintain gonadal differentiation into ovaries. With no testes present to activate anti-Mullerian hormone, the Mullerian structure develops uninhibited (forming the fallopian tubes, uterus, cervix, and upper part of the vagina). And with no testes to produce testosterone, the Wolffian structure (which would have formed the epididymis, vas deferens, and seminal vesicle) disintegrates. The ovaries develop normally at first, but because of the missing X chromosome, the egg cells die prematurely and most ovarian tissue degenerates before birth.

With no SRY activation and no anti-Mullerian hormone, the fetus develops anatomy to support the production of large gametes. Thus, newborns with Turner syndrome are females.

More than 50% of females with 45,X are not diagnosed at birth. Instead, many diagnoses of Turner syndrome occur during childhood and into puberty when the physical differences become more apparent. Like Klinefelter's, the diagnosis for Turner syndrome uses karyotype testing, where an individual's chromosome composition is analyzed through a blood sample.

The missing X chromosome most commonly results in a loss of ovarian function and unique physical differences. Many affected girls do not undergo puberty unless they receive hormone therapy, and most are infertile. Only a small percentage of females with Turner syndrome retain ovarian function, and an even smaller percentage are able to conceive with advanced fertility treatments. With the donation of an egg or embryo, along with hormone therapy, it is possible for females with Turner syndrome to bear children--though this is relatively high-risk. Aside from loss of ovarian function, affected females experience differences in the appearance of their bodies. For instance, females with Turner's tend to be shorter than their 46,XX female counterparts, they may have extra folds of the skin on the neck, puffiness or swelling of the hands and feet, skeletal differences, and kidney problems. One-third to one-half of affected females are born with heart defects--the complications of which can be life-threatening.

Turner syndrome is a condition which requires lifelong medical treatments, whether it be for hormonal insufficiencies, skeletal disorders, and even cardiac problems. The most common treatment is hormone therapies. During childhood, growth hormones can help increase height and improve bone growth. To begin puberty, most girls with Turner syndrome need estrogen and related hormone therapies, often started around the age of 11. Estrogen helps promote breast development and can improve the volume of the uterus. Like Klinefelter's, speech therapy can increase expressive language skills; tailored support in school can help affected girls develop stronger learning skills; and finally, taking part in group activities can help build social skills.

In all, females with Turner syndrome have a unique set of developmental differences which arise from a missing copy of the X chromosome. Through the application of strong social support, appropriate therapies, and consistent medical treatment, females with 45,X can live a happy and healthy life.

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© 2020 Zachary A. Elliott, All Rights Reserved.