Edwards syndrome (Trisomy 18)

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Edward 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 chromosome eighteens. And so Edwards syndrome is also known as Trisomy 18.
In other words, three chromosome eighteens, 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, now, 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? 5050.
Now, what if someone contributes one too many say dad contributes 23 and mom gives 24. Is that possible?
Well, the short answer is yes. And that'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 birth is Trisomy 18 or Edward syndrome. All right.
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 gonna 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. And even though there are two copies of DNA, here, we'll 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 cell splits 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 up to R 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 the regular two.
Well, with Edwards syndrome or Trisomy 18, a process called non disjunction accounts for most of the cases, non disjunction means that the chromosomes don't split apart.
If the chromosomes in the first step, don't split apart, then one cell ends up with both chromosomes and the other gets none.
Then the final result is two cells with an extra chromosome and two cells missing one non disjunction can also happen in the second step though.
So the first step goes just fine and both cells have a chromosome. But if they don't splitt 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.
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 18 or trisomy 18.
Apart from non disjunction, 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 needs to be chromosome 18. But the other can be any old chromosome.
In this example, the long arm of chromosome 18 translocate over to chromosome 14. And you end up with a hybrid with both long arms and one hybrid with both short arms.
This guy over here with the short arms carries non essential genes or genes that aren't essential to survive, typically is 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 parents DNA. And you've got two normal cases and then these two other 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 there. 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 parents again and you have trisomy 18 here and monosomy 18 here since this one is missing a chromosome 18, if this process were 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. So it has to divide over and over and over and over and over again, producing every kind of cell in the body.
Each of these divisions is called mitosis, non disjunction 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 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.
All right. Now, having an extra chromosome 18, not surprisingly has an effect on almost every organ system in the body.
This extra chromosome leads to overexpression of the genes on that chromosome which causes abnormal development of all types of cells.
Babies with Edward syndrome have severe intellectual disability and failure to thrive. Almost all will have a congenital heart defect, like septal defects, patent ductus, arteriosus or others.
Common gastrointestinal anomalies include omphalocele, which is when some of the bowels herniate out into the umbilical cord and esophageal atresia where the esophagus ends in a blind ended pouch, instead of continuing to the stomach with esophageal atresia, the fetus swallows less amniotic fluid because the fluid has nowhere to go, which leads to polyhydramnios, which means that more fluid sticks around in the amniotic sac.
Other complications include kidney malformations like horseshoe kidneys where the two kidneys fused together during fetal development, resulting in one horseshoe shaped kidney breathing problems due to pulmonary hypoplasia and frequent infections.
Finally, babies with Edwards syndrome have increased risk of developing Wilms tumor or nephroblastoma, which is a type of kidney tumor and hepatoblastoma.
A major risk factor for Edwards syndrome is advancing maternal age. Another important risk factor is family history.
After having one child with Edwards syndrome, the risk of having a second baby with Edwards Syndrome increases and is typically around 1%.
Edwards syndrome is also three times more common in female babies. Now, most of the babies with Edward syndrome do die before birth, but even those that survive, usually die within a few weeks to months after birth, they usually die due to central apnea, which is when the brain stops, sending signals to the breathing muscles and so breathing stops or due to severe cardiac abnormalities.
There's a long list of dysmorphic features as well like microcephaly, which means small head, a prominent occiput, low set ears, cleft lip and palate which are openings in the upper lip or roof of the mouth.
Micrognathia or small jaw, clenched hands with overlapping fingers and rocker bottom feet, which is when the soles of the feet are rounded and smooth like the bottom of a rocking chair.
There are some clues to diagnose Edwards syndrome prenatally. An imaging test using ultrasound can be performed where clinicians look for nuchal translucency, suspicion for Edward syndrome should also be raised if prenatal sonogram shows polyhydramnios.
Certain serum markers also suggest that a baby might have Edward Syndrome during the first trimester, human chorionic gonadotropin or HCG as well as pregnancy associated plasma protein A or PAP A are decreased compared to unaffected pregnancies.
Now, during the second trimester, alpha fetoprotein or a FP and unconjugated estriol or ue three also decrease. But another serum marker inhibin A is typically normal or slightly decreased.
Diagnosis can be confirmed with karyotyping, which visualizes each chromosome. A karyotype can be done before birth with an amniocentesis or at any time after birth with a blood test.
Now, because Edward Syndrome is due to a chromosomal problem, there is no known cure and so treatment is only supportive and focuses on life threatening conditions.
For example, treatment of heart problems and infections. All right, let's quickly recap Edward syndrome or Trisomy.
18 is a chromosomal disorder where a person inherits three chromosome eighteens instead of two, usually as a result of meiotic non disjunction.
The extra chromosome 18 interrupts the normal development and function of various organ systems causing symptoms like congenital heart defects as well as kidney and gi malformations.
Due to these fatal complications. The affected babies usually die before birth and those that survive will have dysmorphic features like microcephaly, low set ears, cleft lip and palate micrognathia and rocker bottom feet.