Down Syndrome – Causes, Symptoms, Diagnosis, Pathology



Down Syndrome, also known as trisomy 21, is a naturally occurring genetic condition in humans. It is characterized by the presence of an extra copy of chromosome 21, resulting in developmental and cognitive differences. Individuals with Down Syndrome typically exhibit distinct physical features, such as almond-shaped eyes, a flattened facial profile, and a smaller nose. This condition varies in severity, affecting each person differently.

The additional genetic material can lead to intellectual disabilities and delays in developmental milestones. While there may be challenges in cognitive and physical abilities, individuals with Down Syndrome often lead fulfilling lives and can achieve significant accomplishments with proper support, education, and inclusion.

Down Syndrome
Down Syndrome

The understanding of Down Syndrome has evolved, moving away from stigmatization and towards embracing the unique abilities and contributions of individuals with this condition. Advances in medical care, educational strategies, and social awareness have improved the quality of life for people with Down Syndrome, allowing them to engage more fully in their communities and lead meaningful lives.


  • As you are 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.
  • Usually, we have 46 chromosomes that we use to neatly organize all our information, depending on how we define an organization. Each of the 46 chromosomes is 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 base of one of the most common chromosomal disorders Down Syndrome.
  • Someone with Down syndrome has 47 chromosomes instead of 46. Specifically, they have an additional copy of chromosome 21, so rather than two; they have three, so Down syndrome is also known as trisomy 21, in other words, three chromosomes 21.
  • Alright, so to package up half the chromosomes into either a sperm cell or an egg cell, you begin with a single cell that has 46 chromosomes, let’s just say we are making an egg cell for the mother, I am just going to show one pair of chromosomes, but recognize 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 are shaped like an even though there are two copies of DNA here, we still say it’s one chromosome since they are hooked together in the middle by this thing called a centromere.
  • OK next the cell splits in two and pulls apart the paired chromosomes, so in each of these cells; you have now got 23 chromosomes. Now the two copies of the chromosome get pulled apart, and the cells split again, which means our 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, equaling 46 chromosomes, and voila nine months down the road you have got yourself, baby.
  • Now, including Down syndrome or trisomy 21, a process called no disjunction 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 including both chromosomes and then another gets none. Then the final result is two cells by an extra chromosome, and two cells missing a chromosome.
  • No disjunction can also happen in the second step though, so the first steps go 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 correct 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, Robertson and translocation account for about 4% of trisomy 21 cases. Translocation, in this case, is a fancy way of saying the move from one place to another; so a part of one chromosome moves and switches places with a part from another chromosome. In that 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 short arms carries just a little bit of, usually non-essential 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, how they replicate, and how 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 would 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 DNA, and you have got two normal cases, and then these two cases are called balanced carriers, and we say it’s balanced because you have got both long arms, and so most of the genes are still here, kind of like a two-for-one deal. 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 have one extra chromosome 21 since the long arms carry most of the genetic material for both chromosomes 14 and 21, and these are missing chromosomes. Now combine these with the other parents again, and you have trisomy 21 here, and monosomy 21 here, since it’s missing a chromosome 21. If this process were switched such that chromosome 14 ended up with the long chromosome first, then you would ultimately end up with trisomy 14 and monosomy 14.
  • So of the 12 possibilities, two end up being trisomy 21 rights? With Robertson a translocation, one of these chromosomes needs to be chromosome 21 right? Even though the other is usually chromosome 14, it can be other chromosomes as well, like chromosome 22. Finally, about 1% of patients are mosaic, meaning their cells are mixed, some have 46 chromosomes and some have 47. How does that happen though? Well, let’s think about what happens after conception.
  • So you have got this one cell, called the zygote that needs to develop into a human, right? Since we are 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 would end up including 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 fewer 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 48 chromosomes, and this cell can’t survive, The other cell, though, loses one of its 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 have ended up with the right amount of chromosomes.
  • So if it happens early in development, you will end up with the normal amount of chromosomes. If it’s late in development though, then fewer 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 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 hearts 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 epicanthic folds. Having an extra chromosome 21 is thought to affect these systems by 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 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 is older than 45 years old. During pregnancy, some screening tests can be done, and certain markers suggest a 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 Aare 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 within the neck area of the fetus. None of these are accurate 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 much greater longevity and quality of life. Many individuals with Down syndrome can thrive and lead full lives.


What causes Down Syndrome?

Down Syndrome is primarily caused by the presence of an extra copy of chromosome 21. This condition is known as trisomy 21 and occurs during the formation of reproductive cells or early in fetal development.

What are the common symptoms of Down Syndrome?

Common symptoms include intellectual disabilities, distinctive facial features, developmental delays, and potential health issues such as heart defects, hearing problems, and thyroid conditions. The severity of symptoms can vary widely among individuals.

How is Down Syndrome diagnosed during pregnancy?

Down Syndrome can be diagnosed through prenatal screening tests like non-invasive prenatal testing (NIPT), chorionic villus sampling (CVS), or amniocentesis. These tests analyze genetic material to assess the risk of chromosomal abnormalities.

What is the pathology of Down Syndrome?

The presence of an extra chromosome 21 disrupts normal development and leads to the characteristic features of Down Syndrome. This additional genetic material affects various bodily systems, resulting in the observed physical and cognitive differences.

Can individuals with Down Syndrome lead fulfilling lives?

Yes, with appropriate support and early interventions, individuals with Down Syndrome can lead fulfilling lives. Specialized education, therapies, and healthcare can help maximize their potential and address specific challenges associated with the condition.


So in This Post, Down Syndrome What other points can you think of/have experienced? Let me know in the comments.

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