What is Down syndrome?

A genetic alteration (an extra chromosome in pair number 21) causes Down syndrome, which causes the baby to be born with a variable degree of mental disability, characteristic physical features, and some associated pathologies.

The syndrome is a genetic abnormality that occurs due to a failure at the time of conception. The average number of chromosomes in humans is 46, distributed in 23 pairs, the last being the sex chromosomes X and Y. The fertilized ovum receives a chromosome from the mother and a chromosome from the father to make up each of the 23 pairs of chromosomes. Still, sometimes an abnormality occurs that consists of an extra chromosome in pair number 21, known as chromosome 21 trisomy.

Chromosome 21 trisomy is the most common chromosomal abnormality: it affects 1 in 700 live-born children of all races, regardless of geographic environment or social class. 

In 95% of the patients with this syndrome, there is a trisomy of chromosome 21 (which means that there are three chromosomes # 21 when the normal thing is that there are only two). The remaining 5% present a chromosomal translocation (a change of fragments of genes between different chromosomes).

This genetic alteration causes the affected baby to be born with a variable degree of mental disability, characteristic physical features, and some associated pathologies that we will see below.

Characteristics of Down syndrome

These patients present a picture with different abnormalities that span several organs and systems.

• Marked muscle hypotonia (lack of strength in the muscles).
• Mental retardation.
• Characteristic physiognomy with epicanthic folds and an upward and outward slanted lid opening (skin fold at the inner corner of the eye) and depressed nasal root.
• Maxillary and palate hypoplasia determines the protrusion of the tongue (the jawbone of the face is poorly formed, and the mouth is small so that the tongue does not fit in it and sticks out).
• Internal abnormalities, mainly of the heart and digestive system: defects of the ventricular septum, patent ductus arteriosus, duodenal atresia, or stenosis (narrowing or lack of development of a part of the intestine).
• Characteristic dermatoglyphics with the simian groove on the palm (altered fingerprint with a transverse fold on the palm, similar to that of the monkey).

Some signs are very frequent or typical, such as muscular hypotonia, dermatoglyphics, and, in the case of light-colored eyes (blue-green), Brushfield spots, small white spots located concentrically in the third inner iris (not seen in dark eyes).

Mental retardation is the most characteristic sign of Down syndrome. Adults usually have an intellectual coefficient (IQ) of 25 to 50. Still, it is considered that the level they are capable of reaching may vary depending on the stimuli that the patient receives from their family and environment. IQ varies during childhood, peaks relative to average between the ages of 3 and 4, and then declines more or less evenly.

From a psychological point of view, patients with this syndrome are cheerful, obedient, have musical sense, and do not tend towards violence. The marked hypersexuality of the patients is characteristic.

From a biochemical point of view, patients have a high level of purines in the blood.

Fertility is different in the two sexes: males with Down syndrome are infertile, while women are fertile. If a patient with Down syndrome has children, the chances of transmitting the disorder to her offspring are 50%. That is, about 50% of her children will be normal. In comparison, the other 50% will suffer from Down syndrome due to the transmission of an excess chromosome 21.

Risk factors for Down syndrome

This relationship between maternal age and trisomy suggests that the origin of this anomaly is in maternal meiosis, which we will explain below. Trisomy 21 preferentially originates from nondisjunction in the mother’s meiosis: fertilization occurs by the union of a paternal sperm and a maternal oocyte. The cell resulting from this union will give rise to the future embryo, which has 46 chromosomes. Both the sperm and the oocyte must have 23 chromosomes (23 + 23 = 46). They must have decreased their genetic information to half, which is done through a process called meiosis.

The frequency of nondisjunction increases correlatively with maternal age; In women, all oocytes are formed at birth, and some of them are activated in successive menstrual cycles until menopause. In contrast, sperm production is continuous throughout the male’s adult life, which does not mean that he is free from nondisjunction occurring in his sperm. Although most trisomies 21 occur due to maternal nondisjunction, a minority of them, 20%, occur due to paternal nondisjunction.

Nondisjunction is a sporadic phenomenon, so if a woman has had a child with Down syndrome due to trisomy, the risk of having another is related only to her age. On the other hand, if a woman has had a sick child due to a translocation, one of the two parents is likely a translocation carrier, and the risk of recurrence (the risk of it happening again) is much higher.