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Edwards syndrome (Trisomy 18)





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Autosomal trisomies: Pathology review
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Edwards syndrome (Trisomy 18)


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High Yield Notes
6 pages

Edwards syndrome (Trisomy 18)

11 flashcards

USMLE® Step 1 style questions USMLE

2 questions

A 37-year-old woman, gravida 2, para 1, comes to the office for the evaluation of abnormal laboratory and sonogram results. She previously had a regular menstrual period every 28 days and is currently at 18 weeks gestation. She regularly takes prenatal vitamins and has no other medical conditions. Vital signs are within normal limits. A fetal anomaly scan performed one week ago was significant for polyhydramnios and intrauterine fetal growth restriction (IUGR). A second trimester quadruple screening test is performed at this visit, and the results are shown below:  

 Laboratory value  Result 
 Maternal serum alpha fetoprotein  Low 
 Unconjugated estriol  Low 
 β-HCG  Low 
 Inhibin A  Low 

Which of the following additional findings will likely be seen on the sonogram in this patient?

External References

Content Reviewers:

Yifan Xiao, MD

Edwards syndrome, named after the British geneticist, John Edwards, who first identified it, is a chromosomal disorder where a person inherits an extra copy of chromosome 18 or a part of it. So instead of having two, they have three chromosomes 18 and so Edwards syndrome is also known as trisomy 18, in other words, “three chromosome 18s”.

All right, our DNA is like this humongous blueprint of information on how to make a human. Usually this massive document is packaged up nicely into a storage bin called a chromosome. Usually we have 46 chromosomes that we use to neatly organize all our information, depending on how you define organize. Each of the 46 chromosomes is actually part of a pair of chromosomes, since you get one from each parent, so 23 pairs. 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, so one from each pair, right? Fifty-fifty. Now, what if someone contributes one too many? Say Dad contributes 23 and Mom contributes 24, is that possible? Yes, and it’s the basis of trisomies, in other words, having three copies of a particular chromosome. Now the most common trisomy in live births is trisomy 21, or Down syndrome. But the second most common trisomy in live births is trisomy 18, or Edwards syndrome.

Alright, so 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 an egg cell for the mother, I’m just going to show one pair of chromosomes, but remember that all 23 pairs do this. So the process of meiosis starts, 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 a sperm cell from dad that has 23 chromosomes as well, totaling to 46 chromosomes, and voila–nine months down the road you’ve got yourself a baby.

OK let’s see how someone can end up with three copies of chromosome 18, instead of two. Well with Edwards syndrome, or trisomy 18, a process called nondisjunction accounts for most of the cases. Non-disjunction means the chromosomes don’t split apart. If the chromosomes in this first step don’t split apart, then one cell ends up with both chromosomes and the other gets none. Then 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 a sperm cell combines with any of these that have a duplicate of chromosome 18, then the combined cell will have three chromosome 18s, or trisomy 18.

Apart from nondisjunction, chromosomal translocation accounts for a small percentage of trisomy 18 cases. Translocation means that a part of one chromosome switches places with a part from another chromosome. One of these chromosomes needs to be chromosome 18 but the other can be any other chromosome. In this example, the long arm of chromosome 18 translocates over to chromosome 14, and you end up with a hybrid with both long arms and one hybrid with both short arms. This guy with the short arms carries nonessential genes, or genes that are not essential to survive and is typically lost by the end of meiosis.

All right, let’s say that these cells replicate and split into one with both normal chromosomes, and one with a chromosome with only long arms and one with only short arms, in which case after splitting again you’d have two normal cells and two cells with a big guy, since we lost the little guy along the way. So now contribute the other parent’s DNA, and you’ve got two normal cases, and then these two cases are “balanced carriers”, and we say they’re balanced because they’ve got both long arms, and so most of the genes are still here. So balanced carriers usually don’t have any symptoms. OK now let’s say the normal chromosome 14 ends up with the short, and normal chromosome 18 with the long. Now you get two cells with the normal and long-arm, and two cells with the normal and short arm, which remember is usually lost. So these ones have one extra chromosome 18, since the long arms carry most of the genetic material for both chromosomes 14 and 18, and these ones are missing chromosomes. Now combine these with the other parent’s again, and you have trisomy 18 here, and monosomy 18 here, since it’s missing a chromosome 18. If this process was switched such that chromosome 14 ended up with the long chromosome first, then you’d ultimately end up with trisomy 14 and monosomy 14. So out of the 12 possibilities, two end up being trisomy 18, and they will have all the symptoms.

Finally, about 1% of patients are mosaic, meaning their cells are mixed, and some have 46 chromosomes and some have 47. So after conception you’ve got this one cell, called the zygote, that needs to develop into a human and so it has to divide, over and over again, producing every kind of cell in the body. Each of these divisions is called mitosis. Nondisjunction of chromosome 18 can also happen during mitosis, in which case you’d end up with one cell that has an extra chromosome 18, and one without, so one with 47 total chromosomes and one with 45. The cell with 45 chromosomes isn’t able to survive, but the one with 47 does survive, and continues to replicate and produce more cells with 47 chromosomes. Mosaic patients usually have less severe symptoms when compared to patients who have trisomy 18 in every cell in their body.