How to detect Down syndrome

The vast majority of persons with Down syndrome have three copies of chromosome 21 in every cell of their body, instead of the usual two. — Filepic

Chromosomes contain protein and DNA (deoxyribonucleic acid), which carry genetic information and are found in the cell nuclei.

They determine how the foetus, and later, the baby, develops and functions during pregnancy and after birth respectively.

Chromosomes are found in pairs and are numbered – every cell in the human body has 23 pairs, half of which are from the mother and the other half from the father.

Down syndrome (previously also known as “mongolism”) is a congenital condition in which a person has an extra chromosome 21.

This extra chromosome affects the development of the foetus, and later, the baby, causing both physical and mental challenges during childhood and adulthood.

The incidence of Down syndrome in Malaysia is not known – it is estimated that Down syndrome occurs once in every 600 to 700 births.

However, the true incidence may be higher as about one quarter to half of foetuses with Down syndrome are spontaneously aborted (i.e. miscarried) in the first and second trimesters of pregnancy.

Different numbers

Although there are different types of Down’s syndrome, the physical features and behaviours are the same.

The different types can be differentiated by chromosomal analysis.

The most common type is Trisomy 21, in which every cell in the body has three separate copies of chromosome 21, instead of the usual two copies.

About 95% of Down syndrome cases are of this type.

Translocation Down syndrome occurs in about 3% of the affected.

This occurs when an extra part of, or an entire, chromosome 21 is present, but is attached (also termed “translocated”) to another chromosome, instead of being a separate chromosome by itself.

Mosaic Down syndrome occurs in about 2% of the affected.

In this case, some of the body’s cells have three copies of chromosome 21, but other cells have the typical two copies, hence the descriptive term “mosaic”, which means mixture or combination.

Their features may be the same as those with the other types of Down syndrome or there may be fewer features.

Risk factors

The extra chromosome 21 usually occurs by chance because of a change in the egg or sperm.

This change is not due to anything done before or during pregnancy.

A factor that increases the risk of an extra chromosome 21 is advancing maternal age.

Mothers who get pregnant at age 35 years or more are more likely to have a Down syndrome foetus than those who get pregnant at a younger age.

The risk increases with increasing maternal age, i.e. the risk is more at 45 years than at 40 years, and lesser at 35 years.

Parents who themselves have an extra chromosome 21 and/or who previously had an affected pregnancy, are also at increased risk, independent of advancing maternal age and spontaneous chromosomal rearrangement.

However, the majority of babies born with Down syndrome are to mothers who are less than 35 years old merely because there are many more births among younger women.

Physical features

The common features of Down syndrome include:

• A flattened face, especially the nasal bridge
• Almond-shaped eyes that slant upwards
• A short neck
• Small ears
• A tongue that tends to stick out of the mouth
• Tiny white spots on the iris of the eye
• Small hands and feet
• A single line across the palm of the hand (palmar crease)
• Small fingers that sometimes curve toward the thumb
• Poor muscle tone, and
• Shorter than average height in childhood and adulthood.

Other common health problems include congenital heart conditions, hearing loss, ear infections, eye diseases and obstructive sleep apnoea (in which breathing suddenly stops during sleep).

Screening tests

There are two types of tests for Down syndrome: screening and diagnostic.

Screening tests provide information about the likelihood of having a Down syndrome foetus.

They do not provide an absolute diagnosis.

They are safe as they are non-invasive.

They are usually offered to pregnant women at increased risk of having a Down syndrome child.

These tests are done in the first and early second trimesters of pregnancy.

The screening tests include an ultrasound examination and measurement of various substances in the maternal blood.

Depending on the number of these substances measured, these tests are termed double, triple or quadruple tests.

The detection rate of these substances depends on the maternal age range of the population tested, choice of markers, cut-off values used and whether ultrasound is also used.

Ultrasound is used to estimate the gestational age of the pregnancy and whether there is fluid behind the foetal neck.

If there is fluid, its thickness is measured (also termed “nuchal fold thickness”).

The normal nuchal fold thickness is related to the gestational age and an increase corresponds to an increased risk of chromosomal and other foetal abnormalities.

Screening tests help determine the foetal risk of Down’s syndrome.

On rare occasions, the tests can give an abnormal result when there is no foetal abnormality (i.e. a false positive).

Sometimes, the tests are normal, even though there is an existing abnormality (i.e. a false negative).

Diagnostic tests

Diagnostic tests can diagnose Down syndrome by checking the chromosomes in a sample of cells.

They are usually offered if the screening tests reveal an increased risk of the foetus having Down syndrome.

As these tests are invasive, there is a small risk of miscarriage with the risk increasing as the pregnancy advances.

These tests are usually done after a screening test reveals that the foetus has an increased likelihood of Down syndrome.

The sample of cells used in chromosomal analysis are obtained by chorionic villus sampling (CVS) or amniocentesis.

CVS, which is done between 10 to 13 weeks’ gestation, involves obtaining a sample from the chorionic villi, which are the part of the placenta that provide nutrients and oxygen to the foetus.

The chorionic villi cells usually have the same number of chromosomes as the foetus.

Amniocentesis, which is done between 15 to 20 weeks’ gestation, involves obtaining a sample from the amniotic fluid surrounding the foetus – the fluid contains foetal cells.

Percutaneous umbilical blood sampling (PUBS), which is done between 18-22 weeks’ gestation, involves obtaining a sample of foetal blood from umbilical cord.

PUBS gives the most accurate diagnosis of Down syndrome.

However, it is not done often as its risks are more than CVS or amniocentesis.

The attending doctors will advise parents prior to, during and after both screening and diagnostic tests.

Adequate information will be given so that parents’ decision-making is informed.

Clarifications and information should be sought from the attending doctors if there are any concerns.

Dr Milton Lum is a past president of the Federation of Private Medical Practitioners Associations and the Malaysian Medical Association. For more information, email [e-mail]. The views expressed do not represent that of organisations that the writer is associated with. The information provided is for educational and communication purposes only, and it should not be construed as personal medical advice. Information published in this article is not intended to replace, supplant or augment a consultation with a health professional regarding the reader’s own medical care. The Star disclaims all responsibility for any losses, damage to property or personal injury suffered directly or indirectly from reliance on such information.