Last edited 06/2020 and last reviewed 04/2021

In 1887 Landon-Down described a syndrome of mental handicap associated with various physical abnormalities and a supposed resemblance to members of the Mongol race. This unfortunately led to this condition becoming known as mongolism but the condition is now known as Down's syndrome or trisomy 21.

A third copy of chromosome 21, trisomy 21, has long been recognized as the cause of Down's Syndrome

  • the 200 to 300 genes on chromosome 21, as well as epigenetic factors, have been identified as contributors to clinical features of the syndrome
  • multiple genes both on chromosome 21 and at other sites in the genome, such as polymorphisms of the Down's syndrome cell-adhesion molecule (DSCAM) and of the amyloid precursor protein gene, contribute to the variation in clinical manifestations
  • Trisomy 21 occurs either by nondisjunction, with the presence of 47 chromosomes, or by translocation of an additional chromosome 21 to another chromosome; the clinical features do not differ between the two causes of trisomy 21
    • mosaicism of trisomy 21 and partial trisomy 21 are other genetic diagnoses and are usually associated with fewer clinical features of Down's syndrome

Down’s syndrome is the most common chromosomal disorder and was prenatally diagnosed in about 2.7 in 1,000 pregnancies in England and Wales in 2013 (1)

  • due to the rate of spontaneous miscarriage/stillbirth or termination following prenatal diagnosis, the live birth prevalence is lower at 1.1 per 1,000 live births
  • Trisomy 21 occurs in all ethnicities
    • the chance of Down’s syndrome is related to maternal age and rises from about 1:1,300 in 25 year olds to 1:380 in 35 year olds, and further to 1:28 in women aged 45 years

The incidence of Down's syndrome, as with other trisomic abnormalities, increases with maternal age. The number of live births to women aged 40+ has doubled, with a 6% increase in fertility seen in 2006 (2).

Note however that mothers of any age can have infants with Down's syndrome and the majority of Down's syndrome babies are born to younger mothers.

In 2018/2019 a new Non-Invasive Prenatal Test (NIPT) was rolled-out in the NHS, with the aim to reduce the number of women who have invasive tests.

Women with a chance equal or greater than 1 in 150 of having a baby with Down’s syndrome, Edwards’ syndrome or Patau’s syndrome are offered the additional option of NIPT. NIPT involves taking a blood sample from the mother and there is no risk of miscarriage (1)

  • NIPT is based on the development of cell-free prenatal screening and parallel sequencing of maternal plasma cell-free DNA (cfDNA)
  • the high specificity of cfDNA for the detection of DS (99.7%) is valuable for a parent who is a carrier of a translocation and for a woman at increased risk for having an affected fetus (3)


  • 1. UK National Screening Committee (2019). Update of a systematic review on prenatal cell-free DNA testing for fetal trisomies 21, 18 and 13 (twin/multiple pregnancies and DNA microarray technology.
  • 2. :
  • 3.Bull MJ. Down Syndrome.N Engl J Med 2020;382:2344-52.