CHROMOSOMAL SYNDROMES: TYPES AND THEIR CAUSES - NEUROPSYCHOLOGY - 2024

The chromosomal syndromes are the result of abnormal gene mutations that occur within the chromosomes during gamete formation or the first divisions of the zygote.

The main causes of this type of syndrome are two: the alteration of the structure of the chromosomes -such as the syndrome of the cat's meow- or the alteration in the number of chromosomes -such as the Down syndrome-.

Chromosomal syndromes types

1- Turner syndrome or monosomy X

Source: Johannes Nielsen

Turner syndrome is a genetic pathology associated with the female sex that occurs as a consequence of the partial or total absence of an X chromosome, in all or part of the body's cells.

The Turner syndrome karyotype has 45 chromosomes, with a 45 X pattern and one sex chromosome absent.

2- Patau syndrome

Source: Rick Guidotti of Positive Exposure at the August 2016 SOFT (Support Organization for Trisomy 18, 13, and Related Disorders)

Patau syndrome is the third most common autosomal trisomy after Down syndrome and Edwards syndrome.

In the case of this syndrome, the genetic abnormality specifically affects chromosome 13; it has three copies of the same chromosome.

3- Down syndrome or trisomy 21

Source: Vanellus Photo

The well-known Down syndrome or trisomy 21 is a genetic disorder caused by the presence of an extra copy of chromosome 21. It is the most common chromosomal syndrome of congenital mental cognitive disability.

To this day, the exact causes that cause chromosomal excess are not yet known, although it is statistically related to a maternal age greater than 35 years.

4- Edward's syndrome

Trisomic hands. Source: Bobjgalindo

Edward syndrome or trisomy 18 is a human aneuploidy characterized by the presence of an additional complete chromosome in pair 18.

This can also occur due to the partial presence of chromosome 18 due to an unbalanced translocation or by mosaicism in fetal cells.

5- Fragile X syndrome

Source: Peter Saxon

Fragile X syndrome is a genetic disorder that is due to a mutation of a gene, which becomes inactive and cannot perform the function of synthesizing a protein.

Despite being one of the most frequent hereditary disorders, it is quite unknown to the general population, so its diagnosis is often erroneous and late.

Normally it affects males, since in females, having two X chromsomes, the second protects them.

6- Cri Du chat syndrome or 5 p

Source: Paola Cerruti Mainardi. Cri du Chat syndrome. Orphanet Journal of Rare Diseases. 1, 33. 2006

Cri du Chat syndrome, also known as the cat's meow syndrome, is one of the chromosomal disorders caused by a deletion at the end of the short arm of chromosome 5.

It affects one in every 20,000-50,000 newborns and is characterized by the cry that these babies usually have, resembling the meowing of a cat, hence its name.

Normally most of these cases are not inherited, but it is during the formation of reproductive cells that genetic material is lost.

7- Wolf Hirschhorn syndrome

Source: Rossjlennox

Wolf Hirschhorn syndrome is characterized by multisystemic involvement, leading to severe mental and growth disorders.

A good part of those affected die during the prenatal or neonatal phase, but some with a moderate affectation can exceed a year of life.

8- Klinefelter syndrome or 47 XXY.

Source: Malcolm Gin (photographer)

This syndrome is due to a chromosomal abnormality that consists of the existence of two extra XX chromosomes and a Y chromosome. It affects men and causes hypogonadism, that is, the testicles do not work properly, which leads to various malformations and problems. metabolic.

These types of aneuploidies in the sex chromosomes are usually relatively frequent. Normally, in half the cases it is due to paternal meiosis I, and the rest of the cases to maternal type II meiosis.

9- Robinow syndrome

Source: Samia A Temtamy, Mona S Aglan. Brachydactyly. Orphanet Journal of Rare Diseases. 3, 15. 2008. DOI: 10.1186 / 1750-1172-3-15

Robinow syndrome is an extremely rare genetic disorder characterized by dwarfism and bone malformations. Two types of Robinow syndrome have been identified, distinguished by the severity of their signs and symptoms and by inheritance patterns: the autosomal recessive form and the autosomal dominant form.

Autosomal recessive inheritance means that both copies of the gene in every cell must have the mutations for the alteration to be expressed. The parents of a subject suffering from this recessive disease have one copy of the mutated gene, but they do not show any signs or symptoms of the disease.

In contrast, autosomal dominant inheritance means that one copy of the altered gene in each cell is sufficient to express the alteration.

10- Double Y, XYY syndrome

Source: http://images.clinicaltools.com/images/gene/trisomyxyy.jpg (Creative Commons Attribution-Share Alike 3.0 Unported)

Double Y syndrome, or commonly called superman syndrome, is a genetic disease caused by an excess of chromosomes. As it is an alteration in the Y chromosome, it only affects males.

Even though it is due to an abnormality in the sex chromosomes, it is not a serious disease, since it does not have alterations in the sexual organs or problems in puberty.

11- Prader WILLY syndrome

Source: Schüle B et al

De Prader Willy syndrome is a rare and non-inherited congenital disorder. In those people with PWS, there is a loss or inactivation of the genes of the 15q11-q13 region of the long arm of chromosome 15 inherited from the father.

Symptoms include muscular hypotonia and eating problems in its first stage (hyperphagia and obesity) from the age of two with somewhat peculiar physical features.

12- Pallister Killian syndrome

Source: Maninder Kaur, Kosuke Izumi, Alisha B. Wilkens, Kathryn C. Chatfield, Nancy B. Spinner, Laura K. Conlin, Zhe Zhang, Ian D. Krantz

Pallister Killian syndrome occurs due to the abnormal presence of an extra chromosome 12 in some cells of the body, giving rise to various musculoskeletal abnormalities in the neck, extremities, spine, etc.

13- Waadenburg syndrome

Source: J. van der Hoeve: Abnorme Länge tränenröhrchen mit Ankyloblepharon. Klinische Monatsblatter für Augenheilkunde Vol. 56, pp. 232-238 (1916) (http://web2.bium.univ-paris5.fr/livanc/?cote=epo0557&p=1&do=page)

Waaedenburg syndrome is an autosomal dominant disease with different ocular and systemic manifestations.

It is considered an auditory-pigmentary syndrome, characterized by alterations in hair pigmentation, changes in the color of the iris, and moderate to severe sensory hearing loss.

14- William syndrome

Source: EA Nikitina, AV Medvedeva, GA Zakharov, and EV Savvateeva-Popova, 2014 Park-media Ltd

William syndrome is characterized by the loss of genetic material on chromosome 7, also called monosomy.

This pathology is characterized by atypical facial alterations, cardiovascular problems, cognitive delay, learning problems, etc.

Causes of chromosome syndromes

-Alterations in the number of chromosomes

All of our cells are diploid, which means that the number of chromosomes is even.

Diploidy assumes that for each chromosome that exists there is another equal, therefore we have two copies of each gene, each in its corresponding place on each chromosome.

When forming an embryo, each of the members contributes a chromosome; X for the female sex or Y for the male sex.

The important thing when there is a reproduction, is that each member of the couple contributes a haploid gamete, so that from each reproductive cell or gamete of each one, the zygote would form, which would once again be a diploid cell (46 chromosomes).

There are several alterations in the number of chromosomes:

Polyploidy

When the number of chromosomes in one or all cells is an exact multiple of the normal haploid number (23), this cell is said to be euploid, that is, it has 46 chromosomes.

Thanks to the different techniques that exist for cell staining, we can count the exact number of chromosomes that there are, and if for some reason the number of chromosomes in a cell or in all cells is an exact multiple of the haploid number and different from the diploid number normal, we talk about polyploidy.

If the number of copies of each chromosome is three, it would be called triploidy, if it is four, tetraploidy…

One of the causes of triploidy may be that an egg has been fertilized by two sperm. Obviously it is not viable in humans, since most end in abortions.

Aneuploidies

Aneuploidies usually happen because in the process of meiotic division a pair of chromosomes does not separate, therefore the gamete or haploid sex cells will have an extra chromosome and it would be repeated.

Monosomies

A monosomy occurs when the gamete does not receive the corresponding chromosome, that is, it does not have its counterpart. This results in the total number of chromosomes being 45 instead of 46.

The only case of viable monosomy is Turner syndrome. It is suffered by one woman in every 3000 born, which is proof that the X chromosome is essential for normal growth.

Trisomies

The most common type of aneuploidy in the human species is called trisomy. Of all the sex chromosomes and chromosome 21 are the most compatible with life.

There are three trisomies of the sex chromosomes that are accompanied by almost normal phenotypes: 47XXX, 47XXY or (Klinefelter syndrome) and 47XYY. The first phenotype is female and the other two are male.

Other alterations that occur in the sex chromosomes are: 48XXXX, Y 48XXYY, etc.

One of the best known trisomies is Down syndrome in the 21st.

The others are not viable for humans, since children who are born alive usually die within a few years of life, as is the case with trisomy of chromosome 13 or Patau syndrome and that of 18.

On the other hand, various syndromes caused by an alteration in the structure of chromosomes can also appear.

-Structural alterations of chromosomes

On some occasions the chromosomes lose or gain genetic material (DNA), which implies a structural modification of the chromosome. We can speak of a deletion when a piece of the chromosome is lost and it disappears from the karyotype (such as the cat's meow syndrome).

But if that piece is not lost, but joins another chromosome, we would be facing a translocation.

As long as there is no loss or gain of genetic material, translocations are considered balanced genetic rearrangements. The most important are the reciprocals and the Robertsonian ones.

- A reciprocal translocation: it is nothing more than an exchange of genetic material.

- The Robertsonian translocation: consists of the union by the centromere of the long arms of two acrocentric chromosomes with loss of the short arms, thus when the two chromosomes merge, only one appears in the karyotype.

On the other hand, we call it inversion if a piece of chromosome remains where it was but oriented in the opposite direction. If the area that remains inverted contains the centromere, the inversion is said to be pericentric. If the inversion is outside the centromere, the inversion is said to be paracentric.

Finally we would have duplication, which happens when a piece of DNA on a chromosome is copied or replicated twice.