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

A summary of the characteristics of Down syndrome, its genetic basis and what it involves.

Humans are our genes, both as individuals and as a species. The human genome contains an estimated 25,000 distinct genes with 3.2 billion DNA base pairs. 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.

Some 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 dispersed repeats, so that about half of our genome is composed of repeated nucleotides with no functionality (or whose functionality has not yet been elucidated).

Within this vast genetic conglomerate, it is to be expected that mutations will occur from time to time. Some are inheritable, others appear de novo throughout the individual's life and others are manifested by epigenetic mechanisms, that is, by the regulation of gene expression through certain mechanisms influenced by the environment. Today we come to bring you all the information that you should know about Down syndromeone of the most widespread genetic conditions worldwide. Do not miss it.

What is Down syndrome?

First of all, it is necessary to lay certain foundations that will dictate the rest of the article. As indicated by the Spanish Federation of Down Syndrome (Down Spain) this condition should not be considered, at least at a social level, as a disease.. This is one of the first necessary steps to end the stigma that has been discriminating 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 predictable evolution. A person with Down syndrome does not necessarily 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 this condition live an average of 60 years supports this.

Thus, 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, cellulitis, and other diseases.such as heart disease, celiac disease, sensory deficits, hypothyroidism and others. Thus, we close this initial section by saying that we are not dealing with a disease, but a condition, or what is the same, one more variant within the possible normality.

Its causes and genetic basis

Beyond terminology of a social nature, 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 have two sets 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 (body) cells means that we have 23 pairs of chromosomes within each nucleus, making a total of 46 chromosomes.which makes a total of 46.

Within these 23 pairs, it should be noted that 22 of them are autosomal and one is sexual. This concept will ring a bell, as 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 remaining chromosomes are numbered based on their size and shape, with chromosome 1 being the largest of all (with 245,522,847 base pairs, 28% of DNA) and chromosome 21 being the smallest (47,000,000 base pairs, with only 1.5% of human DNA).

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

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

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 the gametes "split" their genetic information in half, they form a complete cell when they unite. Thus, the fetus regains the diploidy that will determine each of its non-sex cells for the rest of its life.

The problem is that, sometimes, this "partitioning" of the genome during meiosis is not entirely successful. This is why monosomes can eventually arise, monosomies (lack of a chromosome), trisomies (an extra whole or partial copy of a chromosome in a couple) or even tetrasomies (the presence of four copies of a chromosome in a couple) 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 in other words, within the pair of chromosomes 21 (one male and one female) there is one more copy than there should be, making a total of three. This is not the only trisomy that can occur, since, for example, there are also trisomy 13 and 18, although these conditions are much more associated with miscarriages and neonatal death (almost 70% of miscarriages present alterations in the number of chromosomes).

Why does Down syndrome occur?

At this point, we have already learned that Down syndrome is a trisomy 21, that is to say that chromosome 21 has one copy more than necessary (2+1). In 90% of the cases, this condition arises sporadically, because an unprecedented error occurs in the meiotic division.When an egg or sperm is being formed, sometimes instead of a 21 chromosome it inherits the entire pair. Then, when they join with their other gamete, they give a total of 3 chromosomes 21 (2+1), making a total of 47 chromosomes instead of 46.

In a very small percentage of cases translocations occur.These events are commonly referred to as "familial Down syndrome". We will not go into their particularities because of the genetic complexity they report, but it is enough to know that there are some accessory mechanisms beyond the usual error during gametogenesis.

The future of people with Down syndrome

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

Unfortunately, medical professional sources show a very different paradigm 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 Syndromechildren with Down syndrome are often labeled in the classroom as "handicapped" and, as a result, their inclusion in social activities is prevented and they tend to be marginalized.

The employment situation is not much more favorable, as Down España indicates that almost 95% of people with Down syndrome have a disability. almost 95% of people with this genetic condition are unemployed in this country. in this country. Curiously, most of the contracts that are made in large companies to these people end with their permanent inclusion in the workforce: like all human beings, they are capable of showing methodicity, 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 inside themselves and ask what normality is. In a world where biological gender does not determine identity, where the life expectancy of people with genetic conditions is increasingly higher, and where expression is valued above all else, we are increasingly realizing that the "norm" does not exist..

Therefore, anything outside the midline should not be considered a pathology, whether the underlying picture is genetic, emotional, physical, or whether or not it shows externally. As long as it does not imply death and/or disease per se, every condition that defines the individual should be considered as one more variant of what is to be expected in the enormous spectrum that we human beings are. Only in this way will we allow others to live without preconceptions and prejudices.

Bibliographical references:

• Akhtar, F., & Bokhari, S. R. A. (2020). Down syndrome (Trisomy 21). StatPearls [Internet].
• Article: Is Down syndrome a disease, Down Spain. Retrieved April 16, from 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.