USMLE® Step 1 style questions USMLE
USMLE® Step 2 style questions USMLE
A 17-year-old girl comes to the clinic because she would like to request medication to make her grow taller. She has always been shorter than her classmates and appears young for her age. She receives good grades in school and has many friends. She has never had a menstrual period. Her medical history is noncontributory. Her parents are both of normal stature. She is 140 cm (4 ft 7 in) tall, weighs 43-kg (95-lb); BMI is 22 kg/m2. Her temperature is 37.0°C (98.6°F), pulse is 78/min, respirations are 12/min, and blood pressure is 154/92 mm Hg. Physical examination shows a wide-based neck, short stature, and Tanner stage 1 development of her breasts and genitalia. Which of the following is the most likely diagnosis?
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.
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. 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.
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. 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.
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.