Down syndrome: what it is, what causes it, and associated problems

Human beings are our genes, both individually and as a species. The human genome is estimated to contain about 25,000 different genes with 3.2 billion base pairs of DNA. As astronomical as this figure may seem, the reality is far from it: only 1.5% of all our genetic information is made up of exons that code for specific proteins.

About 70% of human DNA is extragenic and the remaining almost 30% is part of gene-related sequences. Of all this extragenic DNA (formerly known as junk DNA), seven out of 10 sections correspond to sparse repeats, so more or less half of our genome is made up of repeating nucleotides without functionality (or whose functionality has not yet been elucidated).

Within this vast genetic conglomerate, mutations are to be expected from time to time. Some are inheritable, others appear de novo throughout the life of the individual and others manifest through mechanisms epigenetic, that is, by regulating the expression of genes through certain mechanisms influenced by the environment. Today we come to bring you

all the information you need to know about Down syndrome, one of the most widespread genetic conditions in the world. Do not miss it.

• Related article: "6 activities for children with Down syndrome"

What is Down syndrome?

In the first place, it is necessary to lay certain bases that will dictate the rest of the article. As indicated by the Spanish Down Syndrome Federation (Down Spain) this condition should not be considered, at least on a social level, as a disease. This is one of the first steps necessary to end the stigma that has discriminated against non-neurotypical people for centuries.

According to the World Health Organization (WHO), pathology is the alteration or deviation of the physiological state in one or more parts of the body, manifested with characteristic symptoms and with a more or less evolution predictable. A person with Down syndrome does not have to be sick, despite having a lower content of brain neurons and synapses between them. It is possible to be healthy even with this condition, and the fact that people with it live 60 years on average supports this.

So that, Doctors do not "treat" Down syndrome, but rather address the possible pathologies that a person with this genetic condition may develop, such as heart disease, celiac disease, deficits of the senses, hypothyroidism and others. Thus, we settle this initial section by saying that we are not facing a disease, but a condition, or what is the same, one more variant within the possible normality.

Its causes and genetic bases

Beyond social terminology, Down syndrome is a really interesting event from a genetic perspective. We begin by pointing out that human beings are diploid (2n), that is, we present two series of the same chromosome, one inherited from the father and the other from the mother. The diploidy that characterizes each and every one of our somatic cells (of the body) makes us have 23 pairs of chromosomes within each nucleus, making a total of 46.

Within these 23 pairs, it should be noted that 22 of them are autosomal and one sexual. This concept will sound familiar to you, because the biology lessons emphasize that the last two chromosomes are the ones that represent our biological gender: XX corresponds to females and XY to males. The rest of the chromosomes are listed based on their size and shape, with chromosome 1 being the largest of all (with 245,522,847 base pairs, 28% of the DNA) and 21 the smallest (47,000,000 base pairs, with only 1.5% of the DNA human).

When gametogenesis occurs, germ cells divide by meiosis rather than mitosis, giving rise to eggs and sperm with half the genetic information than the rest of cells. These are considered haploid (n), and must be this way for the following reason:

Haploid egg (n) + haploid sperm (n) = diploid zygote (2n)

Meiosis is essential in sexual reproduction, because without it, each time the zygote resulting from fertilization would have more and more chromosome pairs (4n, 8n, etc.). Put more simply, if gametes “split” their genetic information in half, they form a complete cell when they come together. Thus, the fetus recovers the diploidy that will determine each of its non-sexual cells for the rest of its life.

The problem is that, sometimes, this "partition" of the genome during meiosis is not done quite well. Thus, monosomies (lack of a chromosome), trisomies (an extra whole or partial copy of a chromosome in a pair) or even tetrasomy can eventually arise, the presence of four copies of a chromosome where there should be only two.

Down syndrome is considered a trisomy 21, or what is the same, within the couple of chromosomes 21 (one male and one female) there is one more copy than it should, making a total of three. It is not the only trisomy that can happen, because for example there are also trisomy 13 and 18, although these conditions are much more associated with abortions and neonatal death (almost 70% of abortions present alterations in the number of chromosomes).

• You may be interested in: "Chromosomes: what are they, characteristics and how they work"

Why does Down syndrome occur?

At this point, we have already learned that Down syndrome is a trisomy 21, that is, that chromosome 21 has one more copy than necessary (2 + 1). In 90% of cases, this condition arises sporadically, as an unprecedented error occurs in the meiotic division: When an egg or a sperm is forming, sometimes instead of a chromosome 21 it is inherited by the entire couple. So, when paired with their other gamete, they give a total of 3 chromosomes 21 (2 + 1), making a total of 47 chromosomes instead of 46.

Translocations occur in a very small percentage of cases, events that receive the common name of “Familial Down Syndrome”. We are not going to go into their particularities due to the genetic complexity they report, but it is enough for us with knowing that there are some accessory mechanisms beyond the error to use during the gametogenesis.

The future of people with Down syndrome

People with Down syndrome are more present in society than it seems, because this genetic condition occurs in up to one in every 700-1,000 live births and about 8 million people around the globe live with it. The average life expectancy is around 60 years (while a few decades ago this figure was less than 10 years), so the number of people with trisomy 21 is expected to increase in the world.

Unfortunately, professional medical sources show a very different paradigm when we speak on a case-by-case basis. According to the study The Efficiency of Motor Activities Programs in Fighting the Social Exclusion of Children and Young People with Down Syndrome, infants with Down syndrome are often classified in the classroom as "disabled" and, therefore, their inclusion in social activities is prevented and they tend to be marginalized.

The employment situation is not much more favorable, since Down Spain tells us that almost 95% of people with this genetic condition of legal age are unemployed in this country. Interestingly, most contracts made in large companies to these people end with their inclusion indefinitely on staff: like every human being, they are capable of showing methodicality, rigor and commitment.

A final thought

As interesting as it is to dissect the genetics of syndromes, we must not forget that we are talking about people at all times. Therefore, we urge readers to look within themselves and ask what normality is. In a world where biological gender does not determine identity, where the life expectancy of women people with genetic conditions is getting higher and where the expression is valued above everything, every time we realize more that the "norm" does not exist.

For this reason, something that falls outside the midline should not be considered a pathology, whether the underlying condition is genetic, emotional, physical, or whether or not it is shown externally. As long as it does not imply death and / or disease per se, any condition that defines the individual must be considered as one more variant than expected in the enormous spectrum that we human beings are. Only then will we let the rest live without preconceptions and prejudices.

Bibliographic references:

• Akhtar, F., & Bokhari, S. R. TO. (2020). Down Syndrome (Trisomy 21). StatPearls [Internet].
• Article: Is Down syndrome a disease?, Down Spain. Picked up on April 16 in https://www.sindromedown.net/noticia/articulo-es-el-sindrome-de-down-una-enfermedad/
• Kazemi, M., Salehi, M., & Kheirollahi, M. (2016). Down syndrome: current status, challenges and future perspectives. International journal of molecular and cellular medicine, 5 (3), 125.