Down syndrome (trisomy 21) – causes, symptoms, diagnosis, & pathology

Down syndrome (trisomy 21) – causes, symptoms, diagnosis, & pathology


As you’re probably well-aware, 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 one of the most
common chromosomal disorders—Down Syndrome. Someone with Down syndrome has 47 chromosomes
instead of 46, specifically they have an extra copy of chromosome 21, so instead of two,
they have three, so Down Syndrome’s also known as trisomy 21, in other words, “three
chromosome 21s”. 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. Now, with Down Syndrome or trisomy 21, a process
called nondisjunction accounts for about 95% of 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 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 21, then the combined cell will have one extra
copy of chromosome 21, in other words, “three chromosome 21s”, or trisomy 21. In case you were wondering, the sperm could
also combine with these cells that have the missing chromosome, if that’s the case then
there would be a total of only one chromosome 21, and we would call it monosomy 21. In my example, we followed the egg cell from
the mother, but this process could happen the opposite way where the sperm starts out
with too many or too few copies of chromosome 21. Apart from nondisjunction, Robertsonian translocation
accounts for about 4% of trisomy 21 cases. Translocation, in this case, is a fancy way
of saying move from one place to another; so a part of one chromosome moves and switches
places with a part from another chromosome. In this case, the long arm of chromosome 21
translocates over to chromosome 14, and you end up with two hybrids, one with both long
arms and one with both short arms. This little guy with the short arms carries
just a little bit of, usually nonessential genetic information, and is typically lost
by the end of meiosis. So there are a few ways this can go down,
first, including the translocated chromosomes, they replicate, and now these could split
into one with both normal chromosomes, and one with the long guy and short guy, 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 a two normal cases, and then these two cases are called “balanced carriers”,
and we say it’s balanced because you’ve got both long arms, and so most of the genes
are still here, kind of like a two-for-one deal. K now let’s say the normal chromosome 14
ends up with the short, and normal chromosome 21 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 21,
since the long arms carry most of the genetic material for both chromosomes 14 and 21, and
these ones are missing chromosomes. Now combine these with the other parent’s
again, and you have trisomy 21 here, and monosomy 21 here, since it’s missing a chromosome
21. 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 of the 12 possibilities, two end up being
trisomy 21 right? With Robertsonian translocation, one of these
chromosomes needs to be chromosome 21 right? Even though the other is usually chromosome
14, it can actually be other chromosomes as well, like chromosome 22. Finally, about 1% of patients are mosaic,
meaning their cells are mixed, and some have 46 chromosomes and some have 47. How does that happen though? Well, let’s think about what happens after
conception. So you’ve got this one cell, called the
zygote, that needs to develop into a human, right? Since we’re not single celled organisms,
it has to divide, over and over again, essentially producing every kind of cell in the body. Now, each of these divisions is called mitosis. Nondisjunction of chromosome 21 can also happen
during mitosis, in which case you’d end up with one cell that has an extra chromosome
21, 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. If this happens early on in development, then
you can imagine that a lot of cells down the line can have 47 chromosomes, right? If it happens later on, then less cells will
have 47 chromosomes. Mosaics can also happen when the zygote starts
with trisomy 21, or 47 total chromosomes. In this case, nondisjunction would produce
one cell with another extra chromosome 21, so this one has four chromosome 21s, totaling
to 48 chromosomes, and this cell can’t survive, The other cell, though, loses one of it’s
three chromosome 21s, so now it has 46 chromosomes, which happens to be the normal amount of chromosomes,
right? And this is sort of like the opposite situation,
because now, through a mistake, you’ve actually ended up with the right amount of chromosomes. So if it happens early in development, you’ll
actually end up with the normal amount of chromosomes. If it’s late in development though, then
less cells will have the normal 46 chromosomes. Having an extra chromosome 21 is one of the
most common chromosomal disorders and not surprisingly it has an effect on almost every
organ system in the body, and for that reason there’s a long list of common issues for
those affected with down syndrome. Here are some of the major ones: septal defects
in the heart’s chambers (usually between the two atria), duodenal atresia, increased
risk of acute lymphoblastic leukemia, mental retardation and increased risk of Alzheimer’s,
and sterility in males. There are several physical characteristics
as well, like a simian crease in the hands, a gap between the first two toes, a flat facial
profile, and epicanthal folds. Having an extra chromosome 21 is thought to
affect these systems by an overexpression of genes on chromosome 21, since there’s
an extra copy contributing to gene expression which changes the development of all the systems
just listed. Now a major major risk factor for down syndrome
is maternal age, the age of the mother. Trisomy 21 happens about once in about 1500
births where the mother is younger than 20 years old, contrasted to about one in 25 births
where the mother’s older than 45 years old. During pregnancy, some screening tests can
be done, and certain markers suggest higher risk that a baby might have down syndrome. Alpha-fetoprotein or AFP, unconjugated estriol
or uE3, are on average lower when compared to unaffected pregnancies, and human chorionic
gonadotropin, or hCG, as well as inhibin A are both typically elevated compared to unaffected
pregnancies. An imaging test, using ultrasound, can also
be performed, where clinicians look for nuchal translucency, literally seeing how much light
passes through the neck area of the fetus. None of these are exact indicators of Down
syndrome, however, but they do give valuable information about the overall risk of Down
syndrome. Even though there’s a long list of complications
and hardships for people with down syndrome, improved medical care has led to a much greater
longevity and quality of life. Many individuals with down syndrome are able
to thrive and lead full lives. Thanks for watching, you can help support
us by donating on patreon, or subscribing to our channel, or telling your friends about
us on social media.

100 comments

  1. Very interesting . In my job I care for some people with Down Sydrome . They do live very full and happy lives . Most of them that I know of are almost able to live independantly because they are more capable than what many people realise.

  2. In robertsonian syndrom 21 trysomy occur so 14 cromosome monosomy does not occur with it…
    So cromosome are 46 obtain same

  3. Big fan of Osmosis but a bit more on signs symptoms and complications of Down's Syndrome and perhaps the pathology leading to those signs/symptoms/complications would have been more useful

  4. U saved my exam ! I looked everywhere for an explanation of 21 trisomy when its related to rob trans and u only had the answer.. A perfect n detailed answer.. Keep it forward <3

  5. I don't understand this!? I just came here to know what is down syndrome and I didn't know it would be so much

  6. Just a FYI, simian crease is now referred to as single palmar crease (more medically accurate and also culturally appropriate).

  7. https://m.facebook.com/story.php?story_fbid=217171258988346&id=207735333265272
    Down Syndrome Documentary

  8. I’m so glad this video was made, I’m doing research on Down syndrome because my baby cousin might have it and I really want to learn more about what it is

  9. this track is really πŸ”₯ . i actually produce a lot of similar instrumentals. id be down to work on a record with you – let me know

  10. Definitely fix the 'mental retardation' note. Very outdated, I thought the information in the video was great, but this ruined it for me.

  11. From 1:57 onwards I’m lost. Is the X one chromosome or one pair of chromosomes? And why are there two shown? And I don’t understand why and how and when they split. And why are there so many sperm cells shown? Totally confused.

  12. Down syndrome can be diagnosed in Fetal USG in 11th-14th week gestation. Nuchal translucency more than 3. Very high beta HCG in maternal blood.

  13. Hi, I was wondering if I could use some of your video in a presentation I have for biology class. I really dig the visualizations and they made a lot of stuff clearer. I will credit the channel of course. Liked and subbed

  14. Can you please clarify whether non-disjunction in DS is a failure with meiosis or mitosis? I understood that non-disjunction with meiosis will lead to trisomy involving sex chromosomes and with mitosis will lead to trisomy involving autosomes (as is the case involving 21st pair in DS).

  15. My biology presentation is due in 5 days and I haven't started πŸ˜…πŸ˜… 4 minutes speech and 1 minute video on down syndrome. If anyone can help me please reply

  16. i have to make a presentation on Down syndrome for my child development class and we're presenting next week….Β I'm so confused by the three types of down syndrome but this video helped a little

  17. I don't get genetics. My grandpa who passed away had blue eyes. My nan is not bald. Thomas Lenhardt has brown eyes and is bald. An official victory. Kevin Lee lost 2 out of his last 3 fights after being really tough against Tony Ferguson. Tony Ferguson almost broke his arm.

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