Edwards syndrome

Edwards syndrome

August 15, 2019 13 By Bertrand Dibbert


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much more. Try it free today! 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. Actually, 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, Robertsonian 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. 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 Edwards syndrome have severe intellectual
disability and failure to thrive. Almost all will have a congenital heart defect,
like septal defects, patent ductus arteriosus, and others. Common gastrointestinal anomalies include
omphalocele, which is when some of the bowels herniate out into the umbilical cord, and
esophageal atresia, where the oesophagus 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 and that 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 fuse together during fetal development resulting
into 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 3 times more common
in female babies. Now most of the babies with Edwards syndrome
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 is 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 Edwards syndrome should also
be raised if prenatal sonogram shows polyhydramnios. Certain serum markers also suggest that a
baby might have Edwards syndrome. During the first trimester, human chorionic
gonadotropin, or HCG, as well as pregnancy-associated plasma protein A, or PAPP-A, are decreased
compared to unaffected pregnancies. Now, during the second trimester, alpha-fetoprotein,
or AFP, and unconjugated estriol, or uE3 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 Edwards 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. Edwards syndrome, or trisomy 18, is a chromosomal
disorder where a person inherits three chromosomes 18, instead of two, usually as a result of
meiotic nondisjunction. 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. Those that survive will have dysmorphic features
like microcephaly, low-set ears, cleft lip and palate, micrognathia, and rocker bottom
feet.