Medicina de precisão do Hospital Israelita Albert Einstein

Chromosomal disorders

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The events that result in the formation of zygotes can occur unexpectedly, generating the so-called chromosomal disorders. These are diverse conditions, originated by a set of mechanisms, which although caused by genetic alterations, are not always hereditary.

Want to understand what chromosomal disorders is? Follow our text to know this and other information!

What are chromosomal disorders?

Chromosomal Syndromes, also called Chromosomal Disorders, are characterized by variation in the structure or number of chromosomes. 

In general, humans have 23 pairs of chromosomes, 22 of which are called autosomes and 1 called an allosome (or sex chromosome ). These macromolecules, made up of DNA and proteins , are present in the nucleus of all living human cells, with the exception of red blood cells.

Despite this, some people may have different amounts of chromosomes (called aneuploidy ) or differences in their structures . These changes are responsible for giving rise to chromosomal disorders.

These disorders comprise a set of varied conditions, whose clinical significance varies according to the extent to which the chromosomes are affected. 

As we will see below, the alterations responsible for chromosomal disorders can be inherited or, more commonly, generated during the formation of gametes.

What causes chromosomal disorders?

Although in some cases they can be hereditary, chromosomal disorders are more commonly caused by random events that occur during gamete or zygote formation.

Aneuploidies, for example, occur during gamete formation, such that chromosomes are incorrectly segregated during meiosis. 

This failure of chromosomal separation is called non-disjunction and it can happen during meiosis 1 or 2, as shown by the figure below.

Most mammals are diploid. This means that humans, for example, have two copies of each chromosome (2n). Nondisjunctions can result in gametes with only one or more than two copies of the same chromosome (n; 3n, 4n).

When used in the formation of a zygote, this gamete affected by nondisjunction can give rise to offspring with one or more additional chromosomes. More rarely, these offspring may be missing a chromosome, a condition called monosomy . 

Chromosomal disorders generated by structural changes in chromosomes, although less frequent, may originate from any of the following mechanisms:

  • Deletion;
  • Duplication;
  • Inversion;
  • Insertion;
  • Translocation.

One type of translocation, called a Robertsonian, is especially relevant to the clinical context. In this event, which only happens with acrocentric chromosomes (13, 14, 15, 21, and 22), two chromosomes lose their short arms and have their long arms joined at the centromere.

This type of translocation can occur in phenotypically healthy individuals, since the lost short chromosome arms may contain little genetic material. On rare occasions, however, Robertsonian translocations can give rise to aneuploidies, being observed in some cases of Down Syndrome, for example.

Chromosomal disorders

Know some chromosomal disorders

As previously mentioned, aneuploidies are the most common cause of chromosomal disorders. Many of its forms are even incompatible with life, especially when the chromosomal alteration occurs in autosomes.

Turner Syndrome, for example, is one of the few forms of complete monosomy of sex chromosomes that does not produce stillbirths. Trisomies, in turn, are the most common form of aneuploidy in humans, being identified in 0.3% of all births.

Down Syndrome

Down Syndrome (DS) is a genetic condition characterized by a karyotype with 47 chromosomes. This extra autosomal chromosome is specifically a third copy (trisomy) of chromosome 21 (in whole or in part) and therefore this condition is also known as “trisomy 21”.

This is the clinical condition most commonly generated by trisomies and aneuploidies in general. Initially described by John Langdon Down in the 19th century, this condition was only categorized as a chromosomal disorder in the 1960s by Jerome Lejeune. 

The aneuploidy from which the syndrome results is usually from meiotic nondisjunction in meiosis 1 or meiosis 2. 

Despite this, Down Syndrome can be originated, more rarely, by a Robertsonian translocation, in which the individual has 46 chromosomes, but one of the pairs of chromosome 21 is dysfunctional.

Edwards’ syndrome 

Edwards’ Syndrome (ES) is also categorized as a trisomy. Individuals with this condition have a karyotype with 47 chromosomes, in which the extra chromosome comes from a non-disjunction that occurred with chromosome 18.

As with Down Syndrome, some of those affected may have Mosaic Edwards Syndrome . This means that not all of these individuals’ cells are affected by trisomy 18. 

In these cases, the phenotypic manifestations are usually milder than in typical Edwards Syndrome.

Patau‘s syndrome

The third most common autosomal trisomy, right after DS and SE, is called Patau’s Syndrome . Like most aneuploidies in autosomes, Patau’s Syndrome is caused by meiotic nondisjunctions, particularly of chromosome 13. 

Therefore, this condition is also called Trisomy 13 . It can also be observed, rarely, in mosaic form and is considered more severe and lethal compared to the other previously mentioned trisomies: about 9 out of 10 affected individuals do not survive the first year of life.

Turner Syndrome

Turner Syndrome is the only known complete form of monosomy: individuals with this condition most often have a 45,X type karyotype. known complete monosomy in humans.

Some women (~15%) also have mosaic karyotypes, such that some of their cells have a 45 karyotype; X, while other cells have a different setting (such as 46;XX or even 47;XXX). 

About 20% of affected people also have X isochromosomes (q or p arm) and ring chromosomes.

Despite the fact that it is a well-characterized condition, most women end up being diagnosed during their youth. In addition, a considerable portion of women are diagnosed only in adulthood and others go their whole lives without being diagnosed.

klinefelter syndrome

Klinefelter Syndrome is the most common sex chromosome disorder in humans. Individuals with this condition are characterized by karyotypes containing an extra sex chromosome (trisomy), predominantly in the 47,XXY form.

It is estimated that only a fraction of affected individuals are diagnosed at some point in their lives and, as with other chromosomal disorders, this condition can present as a mosaic.


Chromosome disorders are genetic conditions characterized by variation in the number or structure of an individual’s chromosomes. This means that they can be divided into aneuploidy (numerical) and structural.

In both cases, some mechanisms (such as non-disjunction) are able to explain how certain genotypes can arise. Some examples of chromosomal syndromes are: Down Syndrome, Patau Syndrome and Klinefelter Syndrome.

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