Trisomy 21 is the most common chromosomal abnormality among liveborn infants. It is one of the most common causes of intellectual disability. The syndrome is characterised by severe learning difficulties, dysmorphic facial features as well as a number other traits. The syndrome results from the child inheriting three copies of chromosome 21 instead of the normal two copies.
Trisomy 21 is more common in boys and occurs on average in 1/650 live births. The likelihood of bearing a child with the condition increases with increasing maternal age. A mother who is <25 years old has a 1/1500 chance of having a baby with trisomy 21 where as a mother who is >45 years has 1/30 chance of their child developing the condition.
However, 80% of babies with the syndrome have a mother who is under 35 years of age because this is when the majority of births take place.
Although the main genetic risk factor for developing the condition is increasing maternal age, many environmental risk factors have been identified. These include exposure to harmful substances during pregnancy such as cigarette smoke, radiation and pesticides.
Chromosome 21 is smaller than other chromosomes but still contains many genes important for the development of the heart, the brain and the development and regulation of metabolism. This extra copy of chromosome 21 causes deregulation of gene expression and results in a reduction in intellectual functioning.
Many children with the condition meet the developmental milestones later than normally expected.
There are three ways of inheriting an extra copy of chromosome 21:
This is the most common method and accounts for 94% of cases. All cells have three copies of chromosome 21. The risk of this abnormality occurring increases with increasing maternal age.
During meiosis, the pair of chromosome 21’s fail to separate so one gamete receives 2 copies. At fertilisation this meets a normal gamete (containing one copy of chromosome 21) forming a zygote with three copies of chromosome 21. However, 50% of zygotes formed with three chromosome 21’s spontaneously abort at this stage.
2) Translocation (5%)
One copy of chromosome 21 is translocated on to another chromosome, most commonly chromosome 14 (see Figure 2).
3) Mosaicism (1%)
Some of the cells have three copies of chromosome 21. This usually arising after the zygote is formed and is thought to occur from non-disjunction at mitosis. This causes a milder form of the syndrome.
Hands and Feet
Problems in the long term:
*Possible OSCE Station 1 - Speaking to a Mother about tests for Down’s Syndrome
Pregnant women should be offered screening for the condition regardless of their age. Screening techniques must have a detection rate >75% and a false positive rate of <3%. This must be explained to the women before consenting to the test.
Measurements which form part of the tests are carried out at ultrasound scans or by a maternal blood sample.
Antenatal Tests for Trisomy 21
1) Used between 10 weeks 3 days and 13 weeks 6 days:
The Combined Test (It can detect around 86% of trisomy 21’s.)
2) Used between 15 weeks 0 days and 20 weeks 0 days weeks:
The Triple Test
The Quadruple Test
The Integrated Test
Once the test has been carried out, the risk of the child having trisomy 21 is calculated taking into account the maternal age and gestation of the baby.
This is usually expressed as a ratio. A 1/250 chance of the baby having Down’s syndrome is a screen positive result.
If the screen result is positive, the next step is to offer a diagnostic test.
There are 2 diagnostic tests:
Inform women of risk to fetus, that other chromosomal abnormalities may be detected and that no clear results may be obtained.
THE MOST IMPORTANT ISSUE REGARDING AMNIOCENTESIS OR CVS IS: WILL A POSITIVE RESULT CHANGE ANYTHING FOR THE PARENTS? IF THE MOTHER DOES NOT WANT AN ABORTION REGARDLESS, THEN THE RISK OF MISCARRIAGE DUE TO THE PROCEDURE MAY OUTWEIGH ANY BENEFITS.
*Possible OSCE Station 2 - Explaining to a Mother about Down’s syndrome
Aims to help them:
A multi-disciplinary approach is important when managing the medical, developmental and social problems faced by these children. Although most individuals with Down’s syndrome are born healthy, they need to be monitored by a paediatrician as they are at risk of developing several conditions. Many specialties are involved including cardiologists and ophthalmologists. Other team members include speech therapists to aid speech and language development, a dietician and occupational therapists and physiotherapists. This approach is used to help the child live as normal a life as possible. In addition, there are many support groups that can give advice.
Despite the initial mortality rate being increased in the first year of life, most children with Down’s syndrome can expect to live until 50-55years.
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Megarbane, A., Ravel, A., Mircher,C., Strurtz, F., Grattau, Y., Rethore, M.O., Delabar, J.M. and Mobley, W.C.The 50th anniversary of the discovery of trisomy 21: the past, present, and future of research and treatment of Down syndrome. Genet Med. 2009 Sep; 11(9):622-3
Sherman, S.L., Freeman, S.B., Allen, E.G.,and Lamb, N.E Risk factors for nondisjunction of trisomy 21. CytogeneticGenome Research 111:273–280 (2005)
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