Trisomy 21 (Down’s Syndrome)

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:

1)      Non-disjunction

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.  

Clinical Features


  • Flat occiput
  • Hypotonia


Facial Appearance

  • Round face
  • Upward slanting eyes
  • Epicanthic folds (extra skin fold covering inner corner of eyes)
  • Brushfield (white spots) spots on the iris
  • Increased gap between the eyes
  • Tongue protrusion
  • Small ears


Hands and Feet

  • Single palmar and sole crease
  • Curved 5th finger
  • Short, stubby fingers
  • Sandal’s gap (increased space between first and second toe)


  • Cardiac abnormality - most commonly atrioventricular septal defect (AVSD).
  • GI abnormality - duodenal atresia.


Problems in the long term:

  • Learning difficulties (memory problems, difficulty with concentration, problem solving and understanding)
  • Developmental delay
  • Small stature
  • Respiratory infections
  • Hypothyroidism
  • Hearing problems
  • Ophthalmic problems
  • Increased risk of childhood leukaemia - acute lymphoblastic leukaemia (ALL)
  • Increased risk of developing Alzheimer’s disease


 *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.)

  • Nuchal translucency    (Measurement of the space between the spine and the nape of the neck.  Most babies have some fluid behind the neck but in Down’s  syndrome there is more  fluid present than normal)
  • β-human chorionic gonadotrophin (βHCG)
  • Pregnancy associated plasma protein
  • Women’s age.


2) Used between 15 weeks 0 days and 20 weeks 0 days weeks:

The Triple Test

  • Maternal α-fetoprotein
  • Unconjugated estriol
  • Free or total β-human chorionic gonadotrophin (βHCG).

 The Quadruple Test

  • Maternal α-fetoprotein
  • Unconjugated estriol
  • Free or total β-human chorionic gonadotrophin (βHCG)
  • Inhibin A
  • Mother’s age in second trimester.

The Integrated Test

  • From 1st semester: Nuchal translucency and  pregnancy associated plasma protein
  • From 2nd semester: Quadruple test measurements


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.

Diagnostic Tests

There are 2 diagnostic tests:

  1. Amniocentesis (performed after 15+0)A sample of amniotic fluid is obtained under ultrasound guidance. This is used to measure the fetal α-fetoprotein level as well as culturing cells for karyotyping. Cell culture can take 3 weeks. The risk of fetal loss is 1% compared to women not undergoing the tests.
  2. Chorionic Villous Sampling (can be performed from 11+0 up until 13+6)The placenta is sampled using a transcervical or transabdominal approach under ultrasound guidance. Karyotyping takes 3 days and the α-fetoprotein level takes 3 weeks.  If the result is positive for Down’s syndrome then a termination can be carried out earlier if desired by the mother. The risk of fetal loss rate from the procedure is 4%. Infection and heavy bleeding can also occur. Its advantage is that it can be performed earlier than amniocentesis.

Inform women of risk to fetus, that other chromosomal abnormalities may be detected and that no clear results may be obtained.



*Possible OSCE Station 2 - Explaining to a Mother about Down’s syndrome

Aims to help them:

  • Understand the risk of the genetic condition.
  • Know more about the condition.
  • Understand what it will mean looking after a child with the condition.
  • Assess the risk of passing on the condition to future offspring.



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.


J Collier, M Longmore, T Turmezei, & A Mafi (2009) Oxford Handbook of Clinical Specialties. Oxford University Press.

CG62 Antenatal care: routine care for the healthy pregnant womanNational Collaborating Centre for Women’s and Children’s Health Commissioned by the National Institute for Health and Clinical Excellence March 2008.

Einfeld, S.L. and Brown R. Down Syndrome—New Prospects for an Ancient Disorder The Journal of American Medical Association (JAMA). 2010;303(24):2525-2526.

T Lissauer, & G Claydon, G (1996) Illustrated Textbook of Paediatrics First Edition. Mosby; illustrated edition edition.

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)

Genetic Counselling Website:



Fastbleep © 2019.