Understanding Chromosome 21 and Down Syndrome
September 20, 2023

Understanding Chromosome 21 and Down Syndrome

What is Chromosome 21?

So what is chromosome 21? Containing only around 300 genes, chromosome 21 is one of the smaller chromosomes found in human cells. This equates to just 1-2% of our entire genetic code. The genes present on chromosome 21 provide instructions for making proteins crucial for several essential biological functions. These include proteins that play a role in regulating immune system activity, skeletal muscle growth and development, communication between nerve cells, and proper fetal development in the womb.

Chromosome 21 exists in pairs, with one copy inherited from each parent. Deviations from this, such as having a third copy in every cell, lead to genetic disorders like Down syndrome. The extra genetic material from trisomy 21 disrupts normal development and causes the characteristics of Down syndrome.

What is the role of chromosome 21 in Down syndrome?

Chromosome 21 is important in Down syndrome because an extra copy of this chromosome causes the disorder . In most cases of Down syndrome, chromosome 21 has three copies rather than the usual two.

This additional chromosome produces overexpression of the genes on chromosome 21. This in turn interrupts the typical development of the individual. We still study how the additional chromosome 21 affects the development, but Down syndrome is inextricably linked to the disorder.

How Chromosome 21 Affects Individuals with Down Syndrome

The most common cause of Down syndrome is trisomy 21. Trisomy 21 is when there are three copies of chromosome 21 instead of two. This extra copy of chromosome 21 leads to the overexpression of the genes it contains.

The presence of three copies results in amplified production of the proteins coded by the genes on chromosome 21. This surplus of proteins interrupts normal development and gives rise to the physical traits and health problems linked with Down syndrome.

The exact mechanisms behind how the extra chromosome 21 causes Down syndrome is still being researched. However, the overexpression of genes on chromosome 21 is believed to create an imbalance that disrupts typical growth and development.

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An extra copy of chromosome 21 is the genetic cause of Down syndrome. There are 23 chromosomal pairs in every human cell. There are two of each chromosome in every cell, one contributed by each parent.

Trisomy 21 refers to the presence of three copies of chromosome 21 rather than the usual two. Nondisjunction, an error in cell division, is to blame for this duplicate copy of chromosome 21, which results in a single cell having two copies of chromosome 21 rather than one.

Having an extra copy of chromosome 21 causes the genes it carries to be overproduced. The hallmarks of Down syndrome, such as intellectual impairment and delayed development, result from this overexpression during embryonic development.

Scientists were able to pinpoint its genetic basis once they established a connection between Down syndrome and chromosome 21. The precise mechanisms are yet unknown and are the subject of investigation. The additional copy of chromosome 21 is known to cause developmental delays.


Prenatal Down syndrome testing

Prenatal Down syndrome testing is available for pregnant women who want to check their baby’s risk of the disease. Screening procedures, such as the first trimester combination test or the cell-free DNA test, can predict the likelihood of Down syndrome but are not diagnostic. Amniocentesis and chorionic villus sampling are diagnostic techniques that allow for chromosomal analysis but pose a slight risk of pregnancy problems.

If Down syndrome is detected during pregnancy, families can educate themselves about the condition and plan accordingly. While prenatal testing is voluntary, it allows parents to mentally and logistically prepare if Down syndrome is discovered before birth. Discussions with medical specialists can assist pregnant women in determining whether prenatal testing is the best option for them.

Exploring the Impact of Chromosome 21 in Down Syndrome

The additional copy of chromosome 21 present in Down syndrome causes a 1.5 fold upsurge in the expression of the genes it harbors. This excess expression affects development in various ways:

It disrupts normal growth and proliferation of cells during development. Cell growth, migration and differentiation are affected. It affects the development of the brain and nervous system. Excess proteins disrupt synapse formation, neuron connectivity and brain structure. This impacts cognitive ability. It disrupts development of muscles and bones, leading to low muscle tone and skeletal abnormalities. It affects the normal development of physical features, leading to characteristic facial features and physical growth delays. It impacts the normal development and functioning of organs like the heart. This leads to a higher risk of heart defects.

The downstream effects of having three copies of chromosome 21 ultimately culminate in the symptoms and health issues associated with Down syndrome. Further research is aimed at gaining a deeper understanding of this complex relationship.

How Does the Extra Chromosome Lead to Down Syndrome?

Although it’s not the only one, the main cause of Down syndrome is trisomy 21, which is having three copies of chromosome 21 instead of the typical two copies. In trisomy 21, the extra chromosome comes from an error with cell division. Specifically, a process called nondisjunction results in a reproductive cell with two copies of chromosome 21 instead of one.

When this cell goes to fertilize a normal cell, the resulting embryo ends up with three copies of chromosome 21 in every cell. This chromosome triplication disrupts typical development and leads to the symptoms of Down syndrome. So the root cause is an extra copy of chromosome 21 that then impacts gene expression and protein production, throwing off the complex cascade of proper development.

Is Chromosome 21 the Only Chromosome Involved in Down Syndrome?

Trisomy 21, caused by an extra copy of chromosome 21, accounts for around 95% of Down syndrome cases. However, Down syndrome can also be caused by other issues:

  • Translocation - Part of chromosome 21 breaks off and attaches to another chromosome, resulting in extra chromosome 21 material. 3% of Down syndrome cases is from translocation.

  • Mosaicism - In this case, while some cells have an extra copy of chromosome 21, others don’t have the typical two copies. This mosaic pattern accounts for around 2% of Down syndrome cases.

Trisomy 21 is the most common cause leading to overexpression of chromosome 21 genes but translocations and mosaicism can also lead to Down syndrome. The overexpression of genes on chromosome 21 disrupts development in each case.

Although very rarely, Down syndrome can be caused by a mutation in a specific gene on chromosome 21. This causes it to dysfunction. So while chromosome 21 trisomy is the predominant cause, other chromosomal abnormalities can also result in Down syndrome.

How Does Chromosome 21 Affect Cognitive Development in Down Syndrome?

The extra copy of chromosome 21 present in Down syndrome leads to impaired cognitive development and intellectual disability. There are several ways chromosome 21 trisomy likely impacts brain development:

Excess proteins produced by chromosome 21 genes disrupt proper formation of neuron connections and dendrite development. This affects cognition and information processing. Normal signaling between neurons is affected, impacting learning and memory function. Connections between different regions of the brain may be disrupted. Brain structure and organization is impaired, leading to changes in size/shape of certain brain regions. The hippocampus in particular is affected, impacting memory and learning ability. Neurogenesis and neuron proliferation is disrupted. Fewer neurons are able to reach maturity.

Chromosome 21 overexpression causes cognitive impairment when it comes to brain development. This could affect a person’s speech, memory, learning and problem solving abilities. However, research continues to further explore how trisomy 21 biologically impacts cognitive abilities.

Does the Extra Chromosome in Down Syndrome Affect Physical Features?

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Yes, the extra copy of chromosome 21 leads to overexpression of genes that affects physical features and growth:

  • Bone development is disrupted, leading to skeletal abnormalities and short stature.
  • Low muscle tone (hypotonia) is common due to the effect on muscle development.
  • Characteristic facial features arise due to slowed development of certain skull/facial bones. Facial features include a flat face, smaller nose/ears, upward slanting eyes.
  • Physical growth in utero and after birth is delayed.
  • Some organs, like the tongue, are larger compared to overall body size.
  • Many individuals have short, broad hands and a single crease across the palm.
  • A higher risk of heart defects exists due to improper development.

So while the intellectual disability stems largely from chromosome 21’s effects on brain development, physical characteristics arise due to the disruption of overall growth and organ/tissue development before birth. The overexpression of genes on the extra chromosome trickles down to affect the complex timing of development in many areas.


This article is examined by Clinical Child Psychologist and Ph. D. Researcher Kevser Çakmak, and produced by Otsimo Editorial Team.

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This post does not provide medical advice. See Additional Information.