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Down’s syndrome is caused by an error in cell division that results in an extra copy of chromosome 21. This can occur in three ways: trisomy 21, translocation and mosaicism. This guide explains each cause and why maternal age is the main risk factor.
Down’s syndrome is caused by the presence of an extra copy of chromosome 21 in a person’s cells. In a typical human cell, chromosomes are arranged in 23 pairs, giving 46 chromosomes in total. In Down’s syndrome, chromosome 21 is present three times rather than twice, giving 47 chromosomes. This extra genetic material, present in every cell of the body, alters the way development unfolds. The extra chromosome typically arises from an error in the formation of an egg or sperm cell, known as non-disjunction, which causes chromosome 21 to fail to separate correctly during cell division.
The most common form of Down’s syndrome is trisomy 21, which accounts for approximately 94 percent of all cases. In trisomy 21, every cell in the body contains three complete copies of chromosome 21. The chromosomal error occurs during the formation of the egg or sperm cell, before conception takes place. Once the egg or sperm with the extra chromosome combines with the other parent’s cell at fertilisation, every cell that develops from that point will contain the extra chromosome. The error is random and is not related to anything either parent did.
Translocation Down’s syndrome accounts for around 4 percent of cases. In this form, the extra chromosome 21 material is not present as a separate chromosome but is attached to another chromosome, most commonly chromosome 14. A person with translocation Down’s syndrome still has the extra genetic material from chromosome 21 that causes Down’s syndrome, but the arrangement differs from trisomy 21. Translocation can sometimes be inherited from a parent who carries a balanced translocation, meaning the parent has the correct amount of genetic material overall but arranged differently. Genetic counselling is recommended for families where translocation Down’s syndrome has been confirmed.
Mosaic Down’s syndrome accounts for approximately 2 percent of cases. In mosaicism, not all cells in the body have the extra chromosome 21: some cells have the typical 46 chromosomes and others have 47. This arises from an error that occurs after fertilisation, during the early stages of cell division. Because only some cells are affected, people with mosaic Down’s syndrome may have a slightly milder presentation of some characteristics associated with Down’s syndrome, though this varies considerably between individuals.
The role of maternal age: Maternal age is the only confirmed risk factor for Down’s syndrome. Cross River Therapy confirms that a 35-year-old woman has around a 1 in 350 chance of conceiving a child with Down’s syndrome, a 40-year-old has approximately a 1 in 100 chance and a 45-year-old has approximately a 1 in 30 chance. The risk increases because as a woman ages, her eggs are more likely to undergo non-disjunction during cell division. However, Cross River Therapy also confirms that around 80 percent of children with trisomy 21 or mosaic Down’s syndrome are born to mothers younger than 35, because younger women have more pregnancies overall.
Nothing causes Down’s syndrome preventably: The chromosomal error that causes Down’s syndrome cannot currently be prevented. It is not caused by maternal diet, stress, illness during pregnancy, medication, radiation exposure or any other identifiable lifestyle factor. The Down’s Syndrome Association is clear that parents should not feel guilty or responsible for their child’s Down’s syndrome: it is a random event that can happen in any pregnancy, at any age and in any family. Research into the mechanisms of chromosome non-disjunction continues but there is currently no intervention that can prevent it.
The three types of Down’s syndrome arise through different chromosomal mechanisms but all result in extra chromosome 21 genetic material.
Non-disjunction during egg or sperm formation results in a reproductive cell with two copies of chromosome 21 rather than one. When this cell is fertilised, the resulting embryo has three copies of chromosome 21 in every cell. The error is random and cannot be predicted. It is more likely to occur as maternal age increases because of age-related changes in the way chromosomes separate during egg production.
An extra piece of chromosome 21 material becomes attached to another chromosome, most commonly chromosome 14, during the formation of reproductive cells. The total amount of chromosome 21 material is the same as in trisomy 21 but it is arranged differently. In some cases, translocation occurs because a parent carries a balanced translocation, making it the only form of Down’s syndrome that can be inherited. Genetic testing of both parents is recommended after a translocation diagnosis.
The chromosomal error occurs after fertilisation during early cell division, meaning only some cells end up with an extra chromosome 21. The proportion of cells affected and the distribution across body systems vary between individuals. Some people with mosaicism have a slightly milder presentation, but this is not universal and cannot be predicted from the percentage of affected cells alone.
The exact mechanism behind non-disjunction is not fully understood. Age-related deterioration in the spindle apparatus that separates chromosomes during cell division is thought to be the main reason why older eggs are more prone to the error. Research continues into the molecular biology of chromosome segregation but there is currently no intervention that can prevent non-disjunction from occurring in an individual pregnancy.
For parents who have a child with trisomy 21, the risk of recurrence in a subsequent pregnancy is estimated at around 1 percent higher than the age-related risk. For parents of a child with translocation Down’s syndrome where one parent carries a balanced translocation, the recurrence risk is significantly higher and depends on which parent carries the translocation and which chromosomes are involved. Genetic counselling after any Down’s syndrome diagnosis helps families understand the specific recurrence risk in their situation.
Down’s syndrome is not caused by anything the parents did during pregnancy, by diet, stress, illness, alcohol, smoking, medication, environmental exposure or any other lifestyle factor that has been studied. It is not a punishment, a mistake or the result of any identifiable parental behaviour. The Down’s Syndrome Association emphasises that parents should not seek to identify something they did wrong, because there is nothing to find. The chromosomal error is random.
SENDhelp places specialist SEN teachers, teaching assistants and support staff in schools and provisions across North London, Bedfordshire, Buckinghamshire and Hertfordshire. If your school needs staff experienced with Down’s syndrome, we can help.
For more information on whether Down’s syndrome is inherited, see our article on Down’s Syndrome and Genetics. For information on the three types of Down’s syndrome in more detail, see our article on The 3 Types of Down’s Syndrome.
Down’s syndrome is caused by the presence of an extra copy of chromosome 21, arising from an error in cell division known as non-disjunction. In trisomy 21, which accounts for 94 percent of cases, every cell in the body contains three copies of chromosome 21. The error is random and is not caused by anything either parent did before or during pregnancy.
No. Down’s syndrome cannot currently be prevented. The chromosomal error that causes it cannot be predicted or stopped. Prenatal screening can identify pregnancies with a high probability of Down’s syndrome, but this does not prevent the condition from occurring. Research into chromosome division mechanics continues but there is currently no intervention that can prevent non-disjunction in an individual egg or sperm cell.
No. Translocation Down’s syndrome can occur as a random event without any family history, or it can arise because a parent carries a balanced translocation. Where translocation is confirmed as the cause of a child’s Down’s syndrome, both parents should be offered genetic testing to determine whether either carries a balanced translocation. If a parent does, genetic counselling helps the family understand the recurrence risk and the options available.
Visit our Understanding Down’s Syndrome hub for more guides on causes, diagnosis, education, health conditions and independent living.
The information in this article is provided for educational purposes only and is not intended as medical advice. If you have concerns about Down’s syndrome or any health condition, speak to a qualified healthcare professional. SENDhelp Education Limited accepts no responsibility or liability for any loss or damage arising from reliance on this content. Any links to third-party websites are provided for convenience only and do not constitute endorsement of their content.
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