The Chromosomal diseases Are caused by chromosomal abnormalities, of which the most common is the alteration in the number of sex chromosomes.
They are very frequent and cause a large number of abortions, congenital malformations and mental retardation.
Types of chromosomal abnormalities
Anomalies can be grouped into two basic categories: number and structure anomalies.
Number anomalies
In the nucleus of the cells is our genetic material that is composed of 46 chromosomes and is Diploid , Since it contains 23 pairs of chromosomes Haploids . Each parent provides 23 chromosomes that go into the Gametes And unite in fertilization.
Number anomalies differ depending on the time of gestation in which the anomaly occurred.
Homogeneous chromosomal abnormalities
They are called homogeneous chromosomal abnormalities to those that occur at the time of Meiotic division Or during fertilization.
The meiotic division or meiosis is a type of cellular reproduction that is used to create the gametes. Therefore, if there is a failure in this process, the anomaly will be in the gamete of one of the parents and will expand to all the cells of the zygote when the fertilization takes place.
- Polyploidies. These anomalies are characterized by gametes having more chromosomes than normal and occurring during fertilization. Fetuses with these types of problems usually die before being born or soon after. The most common polyploidies are triploidies in which there are three sets of extra chromosomes (69 chromosomes in total).
- Aneuploidies. This type of anomalies only affects one or two pairs of chromosomes causing it to have a chromosome of more or less, so that a trisomyoma (if they have one more chromosome) or a monosomy can be given (if it has a minus chromosome) . There are only three trisonomies in which the fetus does not die before birth, chromosome 21, 13 and 18. The most frequent aneuploidies are those that affect the sex chromosomes.
- Supernumerary marker chromosomes. This type of anomalies is more rare and is characterized by the presence of small chromosomes, apparently unusable, but that can have serious consequences in the development of the fetus, being able to cause mental retardation and / or malformations.
Mosaics
Mosaic anomalies are those that occur after fertilization, when the cells are reproducing by mitosis to form the body of the fetus. Therefore, the error is not present in all cells, only in those generated during the mitosis in which the error occurred.
Chimeras
Chimeras occur when a zygote Already formed and a Ovum Are joined, so that there is twice as much female genetic material, and half of the cells will have an X chromosome to spare. The diseases that cause the chimeras are very varied, although the most frequent affectation is the sexual ambiguity.
Structure anomalies
Structural abnormalities are less frequent than number anomalies, although the total number of cases is not known, since it is possible to carry the anomaly without it having any visible effect.
Deletions
In the deletions the anomaly consists in the loss of a part of the chromosomal material. The best known are the deletion of the short arm of chromosome 5, which causes the"cat meow"syndrome and the chromosome 4 syndrome, which causes the Wolf-Hirschhorn syndrome .
Translocations
Translocations are the exchange of genetic material between two or more chromosomes. These can be reciprocal, robertsonian or more complex.
- Simple reciprocal translocations. These translocations occur between two non-homologous chromosomes (which are not part of the same pair of chromosomes).
When genetic material is not lost along the way and the material that arrives has no dysfunction, the person has no visible effect, so it is a carrier, but it has a considerable risk of producing poorly formed gametes and that the formed zygote suffers a Aneuploidy.
It is estimated that 1 in 625 people carries a translocation of this type (Briard & Morichon-Delvallez, 2006).
- Robertsonian translocations . These translocations occur between two chromosomes with a specific structure, called acrocentric chromosomes, in which the centromere is displaced towards the short arms, so that the short arms are shorter and the long arms are longer.
The most common are translocations between chromosomes 13 and 14 (t 13; 14 ) And chromosomes 14 and 21 (t 14; 21 ).
The people who carry it do not suffer any illness, but have the risk of their children suffering a trisonomy.
- Complex translocations. These translocations occur at least between three chromosomes. Carrier women may have children, but men often have reproductive problems, such as infertility or subfertility.
Investments
The inversions are a type of alteration that affects a single chromosome and that happens when the chromosome breaks and they reverse their arms.
The investment is called pericentral if the fragment that has been inverted includes the centromere and paracentral if not. This type of chromosomal alteration affects 1 in 1,000 people (Briard & Morichon-Delvallez, 2006).
If the investment is paracentral, nor the person does not have to present any disease and the risk of having children with some chromosomal alteration is the same as that of the rest of the population. However, if the investment is pericentral the risk of having children with any chromosomal abnormality increases.
Insertions
Insertions occur when one segment of a chromosome is inserted into another chromosome or another region of the same chromosome. Carriers do not have to present any clinical manifestations, although they have a higher risk of having offspring with genetic abnormalities.
Isochromosomes
Isochromosomes occur when one of the four arms of the chromosome is lost during one of the divisions. So when the chromosome is re-formed, it has two arms that are equal on one side (short or long) and two unequal arms on the other (long one and short), instead of four equal arms 2 to 2 (two long And two shorts).
The most common isochromosomes are those of the long arm of the X chromosome, the clinical manifestation of this alteration is very heterogeneous, the people who suffer it may have no problem, have minor problems or even develop a Turner syndrome.
Chromosomal diseases
In this section I will talk about the most frequent chromosomal diseases.
Number anomalies
Most anomalies in the number cause the fetus to die before it is born. There are only three anomalies of the number compatible with life, being trisomies (chromosome 21, 18 and 13).
1- Trisomy 21 (Down syndrome)
This trisonomía is the most frequent in the human beings, it suffers 1 of 650 people, and is present in all the societies, independently of the socioeconomic level. The probability of offspring with Down syndrome increases as the age of the mother increases (Briard & Morichon-Delvallez, 2006).
The clinical manifestation of Down syndrome is well known, the people who suffer it have a characteristic dysmorphia with small round skull, short, flat and large nape with excess skin, flattened and short nose, small mouth and broad tongue...
In addition to having these physical characteristics, people with this syndrome also suffer from visceral malformations and Mental retardation . Visceral malformations include cardiac dysfunction (in 40% of cases) and digestive dysfunction (in 30% of cases).
Mental retardation is shared by all individuals with Down syndrome; their IQ ranges from 50 points (mean at 5 years) to 38 (mean at 15 years). The skill in which the deficit is most striking is abstract reasoning.
Their life expectancy is lower than average, especially if they suffer from visceral malformations, although this depends highly on the individual variables of each person, such as their propensity to contract infections.
2- Trisomy 18 (Edwards syndrome)
He Edwards syndrome Is quite serious. Children who suffer from it usually die a few weeks after birth. It is not a frequent syndrome because it has an approximate incidence of 1 per 8,000 children, being more frequent in the girls (with a proportion of 4/1).
As in Down syndrome, the risk of having offspring with this syndrome increases with the mother's age (Briard & Morichon-Delvallez, 2006).
The children who have it present hypotonia, Microcephaly And dolicocephaly, small mouth, pointed ears and a deformation in the feet in the form of"rocker"or"ice ax".
In addition to these physical dysmorphia, they present visceral malformations that affect the heart, digestive tract and / or kidneys, and suffer from Encephalopathy serious.
3- Trisomy 13 (Patau's syndrome)
He Patau's syndrome Is quite rare, with a prevalence of 1 case among 5,000-15,000 people. This is due, among other reasons, to the fact that most fetuses with trisomy on chromosome 13 die before birth. There is also a greater risk of having offspring with Patau syndrome if the mother is older (Briard & Morichon-Delvallez, 2006).
Babies present with characteristic craniofacial malformations, small skull with curved forehead, broad and small nose,"wolf's mouth", low and malformed ears and, occasionally, cebocephaly. Hand deformities, with hexadactyly, and feet, with"rocking"or"piolet"disease are also frequent.
They also present visceral malformations, especially in the brain, although they can also have them in the digestive apparatus, the heart or other organs.
Children with Patau syndrome can not develop normally and usually die at birth, with a mean life of 130 days (Briard & Morichon-Delvallez, 2006).
Structural anomalies
The most known structural anomalies are those that form the cat-meow syndrome and Wolf-Hirschhorn syndrome, both produced by deletions.
4- Deletion of the short arm of chromosome 5 ("cat meow"syndrome)
This syndrome is very rare, affects only 1 in 50,000 people, and its main characteristic is the symptom that gives the name to the syndrome, the cat meow, which is described as a sharp and sad cry that sounds like the meow of a cat.
The children suffer a craniofacial dysmorgia with microcephaly, moon face, much separation between the eyes and small ears. They do not usually have visceral malformations.
5- Deletion of the short arm of chromosome 4 (Wolf-Hirschhorn syndrome)
Wolf-Hirschhorn syndrome is quite rare, with a prevalence of approximately 1 in 50,000, and affects women more than men (Battaglia, 2012).
The main symptoms are malformations (facial and visceral), mental retardation, developmental problems and seizures. People with this syndrome have high foreheads and furrows, broad brows and straight nose (like an old helmet of a Greek warrior), short upper lip and small, retracted chin.
The most frequent visceral malformations are cardiac. The mental retardation is quite serious, his IQ does not exceed 20 points.
References
- Battaglia, A. (May 2012). Wolf-Hirschhorn Syndrome . Obtained from orphan.
- Briard, M., & Morichon-Delvallez, N. (2006). Chromosomal abnormalities. EMC-Pediatrics, 41 (3), 1-13. Doi: 10.1016 / S1245-1789 (06) 47757-X.