Turner syndrome

Definitions & Key takeaways

Turner syndrome is a genetic condition that affects females, typically resulting from the loss of an X chromosome. It can cause a range of physical and developmental features, including short stature, infertility, heart defects, and learning difficulties. Treatment may involve hormone replacement therapy and other interventions to manage associated health conditions.

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Introduction0:00–0:14

Turner syndrome, named after Henry Turner who first described it, is a chromosomal disorder affecting females where one X chromosome is either completely or partially absent.
Now, our DNA is this humongous blueprint of information on how to make a human, which is usually packaged up nicely into 46 chromosomes.

Physiology0:14–2:00

These 46 chromosomes come in 23 pairs - and each pair has one chromosome from each parent. One of these pairs, the sex chromosomes, determines person’s biological sex and it can be composed of either two X chromosomes for females or an X and a Y chromosome for males.So, if you wanted to make another human, first you’d have to find someone that feels the same way, and then you both contribute half of your chromosomes.
In order to package up half the chromosomes into either a sperm cell or an egg cell, you actually start with a single cell that has 46 chromosomes.
Let’s just say we’re making a sperm cell - for simplicity, we’re only going to show one pair of chromosomes, but remember that all 23 pairs do this.
First step is meiosis, which is what produces our sex cells, and the chromosomes replicate, and so now they’re sort of shaped like an ‘X’—even though there are two copies of DNA here, we still say it’s one chromosome since they’re hooked together in the middle by this thing called a centromere.
OK then the cell splits in two, and pulls apart the paired chromosomes, so in each of these cells you’ve now got 23 chromosomes.
Now the two copies of the chromosome get pulled apart, and the cells split again, which means four cells, each still with 23 chromosomes.
Now these are ready to pair up with an egg cell from mom that has 23 chromosomes as well, totaling to 46 chromosomes, and voila–nine months down the road you’ve got yourself a baby.Usually, each parent contributes one chromosome to each pair.

Pathology2:00–2:39

Fifty-fifty. Sometimes though, one parent might contribute one chromosome too many, which is called trisomy, or one chromosome less, which is called monosomy.
Monosomy is what happens in Turner syndrome and it specifically affects the X chromosome. There are three potential karyotype scenarios associated with Turner syndrome.
Most commonly, an entire X chromosome is missing, giving a 45, X karyotype - in other words, the person only has 45 chromosomes, missing one of the X chromosomes.

Nondisjunction2:39–3:33

This can happen as a result of nondisjunction of sex chromosomes during meiosis, and it happens more frequently in sperm cells - but egg cells can also be affected.
Nondisjunction means the chromosomes don’t split apart - so following meiosis, one resulting sex cell ends up with both chromosomes and the other gets none.
Multiply by two, and the final result is 2 cells with an extra chromosome, and two cells missing a chromosome. Nondisjunction can also happen in the second step though, so first steps goes great, and both cells have a chromosome, but if they don’t split apart in the second step, then the final result is one cell with an extra chromosome, one cell missing a chromosome, and two with the right number of chromosomes.
Now, if an egg cell combines with any of these sperm cells that have the missing chromosome, then you have Turner syndrome.The next most common scenario is mosaicism, meaning the individuals have some cells in their body with the 45, X karyotype and others with a 46, XX karyotype.

Mosaicism3:33–4:47

This happens because of an error following conception. So, conception results in a single cell the zygote, that divides, over and over again, essentially producing every kind of cell in the body.
Each of these divisions is called mitosis. Nondisjunction of the sex chromosomes can also happen during any mitosis, in which case you’d end up with one cell line that has three sex chromosomes, so 47 in total, and one cell line missing an X chromosome, so 45 chromosomes in total.
But if the prior divisions progressed normally, there is also one cell line with 46 chromosomes that contributes cells to the developing fetus.
Now, the cell line with 47 chromosomes rarely survive, but the one with 45 does, and continues to replicate and produce more cells with only one X chromosome, along with the 46, XX cell line, leading to a mix of 45, X and 46, XX cells in the body.

Deletion4:47–5:22

The least common karyotype in Turner syndrome is where there’s only a part of the X chromosome missing. Basically, a section of the chromosome - for example the short arm - is deleted at some point during meiosis, but the rest of the chromosome is passed on.
This can also happen at some point during mitosis, and the result is another mosaic karyotype.As far as we know, these errors happen at random, so parents who have a child with Turner syndrome are not at a higher risk than others of having a second child with the same condition.Now, only having one complete X chromosome impacts the female reproductive system by increasing the rate of loss of eggs, which normally happens more slowly.

Signs and symptoms5:22–8:26

By two years of age, none are left, essentially causing “menopause before menarche”. Without eggs, the ovaries fail to develop normally, becoming non-functional, fibrous, “streak” ovaries.
These streak ovaries can’t produce sex hormones, resulting in hypogonadism and low estrogen levels. The body will respond by producing more follicle-stimulating hormone (FSH) and luteinizing hormone (LH) than normal, since these hormones stimulate estrogen secretion by the ovaries.
The X chromosome also carries genes that are important for growth and development of tissues throughout the body. One of these is the short stature homeobox - SHOX for short - gene.
So having a single copy of the SHOX gene results in, you guessed it, short stature. There are also plenty of other unidentified genes on the X chromosome, so individuals with Turner syndrome are predisposed to cardiovascular defects like preductal coarctation of the aorta and bicuspid aortic valve.
They might have kidney issues, specifically a congenital abnormality called horseshoe kidney where the two kidneys become fused during fetal development.
They might also have lymphatic and skeletal abnormalities, and are at higher risk for type II diabetes and hypothyroidism.
Just how many of these abnormalities linked with Turner syndrome are actually present depends on the proportion of cells the person has with the 45, X karyotype.Signs and symptoms of Turner syndrome vary depending on the age of the person and on how much of the second X chromosome is missing.
Infants may be born with lymphedema, or swelling due to a build-up of lymph, in their hands and feet. Many also have lymph-related swelling of the back of the neck, causing a cystic hygroma, which eventually decreases as they age.
This often leaves extra skin on the neck, called neck webbing, which gives the appearance of having a wider than normal neck.
Coarctation of the aorta and a bicuspid aortic valve can cause lower extremity cyanosis, meaning a bluish or purplish discoloration of the lower limbs, and can result in congestive heart failure.
Children with horseshoe kidney are more likely to have urinary tract infections. In adolescents, skeletal abnormalities become apparent, like short stature, a broad chest with widely spaced nipples, low-set ears and arms that turn outward at the elbows, also called cubitus valgus.
Because it causes streak ovaries, Turner syndrome is also the most common cause of primary amenorrhea, which is when a female has not begun breast development by age 13 or hasn’t had menarche by age 15.
As a result, many females with Turner syndrome are infertile.Karyotype analysis is the only way to diagnose Turner syndrome.

Diagnosis8:26–8:58

It can be done before birth via chorionic-villus sampling or amniocentesis. Other tests can be useful for identifying the specific developmental abnormalities caused by Turner syndrome that may be affecting the person.
For example, an ultrasound can show congenital issues like cystic hygroma, cardiac defects, and horseshoe kidney, and a fasting blood glucose test can help detect diabetes.Treatment for Turner syndrome usually involves growth hormone therapy in childhood to promote height and bone growth and sex hormone replacement therapy starting at adolescence to promote breast and uterine development.

Treatment8:58–9:18

In vitro fertilization can make pregnancy possible for some female with Turner syndrome who are infertile.All right, as a quick recap… Turner syndrome is a chromosomal disorder where one X chromosome is either completely or partially absent.

Review9:18–9:56

The most common karyotypes are 45, X and a 46, XX/45, X mosaic, and the impact of the disorder on the growth and development depends on the proportion of cells affected, and on the amount of X chromosome that is missing.
The most common features include streak ovaries, short stature, lymphedema, neck webbing, and congenital heart and renal defects.
Treatment involves growth hormone therapy and sex hormone replacement