Due to trisomy 21. Chromosome 21 is the smallest of the "autosomes" (the non-sex chromosomes): trisomies of the other autosomes tend to be lethal at an earlier stage of embryonic or fetal development, and so are seen much more rarely. Diagnosis of Down's syndrome requires a karyotype, obtainable from pregnancy tissue by chorionic villus sampling (CVS) or amniocentesis. Screening for increased risk in pregnancy can be performed by triple screen or by looking for nuchal translucency at transvaginal ultrasound.

A form of albumin (a protein in the blood) produced only by the fetus, but crosses the placenta and so is detectable in the mother's blood (measured with a serum alpha fetoprotein, as well as being usefully measured in amniotic fluid obtained by amniocentesis. Detectable in higher than usual concentration with certain open abnormalities involving the fetus's brain and spinal cord (namely anencephaly and spina bifida). Present in lower than usual concentration when there is a trisomyin the fetus, such as Down syndrome (or trisomy 21), trisomy 18 or possibly Klinefelter syndrome -- screening for all of which can be done with a triple test.

Known as "FISH". A form of DNA testing for genetic diagnosis in which a special region of a chromosome is stained with a dye that emits colored light when exposed to ultraviolet light. For example, a marker for chromosome 21 will normally show two spots of light, whereas three spots of light would indicate trisomy 21 (Down syndrome). Useful because the technique is accurate with just one cell, making diagnosis possible in an IVF embryo before transfer (see preimplantation genetic diagnosis), and speeding up prenatal diagnosis while awaiting a full karyotype. Being replaced in some labs by comparative genomic hybridisation.

A measurement done at transvaginal ultrasound of tissue in the neck of the fetus; if excessive, it implies a substantially increased risk that the fetus is affected by Down syndrome and Turner syndrome.

'Pregnancy-associated plasma protein A': a protein made by the syncytiotrophoblast of the placenta to increase its sensitivity to grow. Found in increasing levels in the pregnant woman's serum as pregnancy develops. Decreased if the pregnancy is affected by Down syndrome, therefore measured in the triple test used for fetal trisomy 21 screening.

Measurement of alpha fetoprotein in blood serum. High levels can indicate a birth defect involving the brain or spinal cord, such as anencephaly or spina bifida (confirmed if amniocentesis shows high AFP levels in the amniotic fluid). Low levels can indicate an increased risk of Down syndrome (or trisomy 21), trisomy 18 and, occasionally, Klinefelter syndrome, signaling the need for a karyotype of the fetus's tissues by chorionic villus sampling (CVS) or amniocentesis.

Measurement of human chorionic gonadotropin in serum: essentially a pregnancy test, but carried out more precisely (quantitatively) than is the case with a yes or no test (which is qualitative). Often carried out serially, to determine if a pregnancy is: thriving (hCG levels double every two or three days in normal early pregnancy; languishing (levels rise more slowly, seen with an ectopic pregnancy and with an inevitable miscarriage); or resolving naturally (levels that are falling). Very high levels are seen with hydatidiform mole. Part of the triple screen used to screen for Down syndrome in early pregnancy.

A screen for congenital abnormalities of the fetus done on the mother's blood serum during pregnancy to look for fetal trisomy, including Down syndrome. The original test comprised measurements of (1) serum alpha fetoprotein (decreased in the trisomies), (2) serum hCG (increased in trisomy 21, decreased in trisomy 18), and (3) serum estriol (decreased in trisomy 21, increased in trisomy 18). Note that only 60% of pregnancies with Down syndrome will be revealed by a triple test. Refinements have taken place, with 'free beta' (part of the hCG molecule) replacing hCG itself, and with the addition of PAPP-A replacing estriol, increasing the sensitivity and specificity of the test. Further gains in sensitivity and specificity comes from adding an ultrasound test for nuchal translucency. Even so, false positive tests are possible, which will be resolved only by performing CVS or amniocentesis, and so also are false negative tests, which means that CVS and amniocentesis should still be considered in otherwise high-risk situations.

An abnormality of the chromosome complement in which there is an extra chromosome seen on the karyotype. The extra chromosome can be an autosome, such as in Down syndrome (trisomy 21), or a sex chromosome, such as triple-X syndrome (47,XXX), Klinefelter syndrome (47,XXY) and extra-Y-chromosome syndrome (47,XYY).

A trisomy for chromosome number 21, or an extra chromosome-21. This is the most common of the trisomies and gives rise to Down syndrome. Research has shown that the commonest source of the extra chromosome is a mistake in the first division of meiosis in the egg cell (during the many years it rests as a primary oocyte).