Trisomy 21, also known as Down syndrome, is a numerical chromosomal anomaly in which the 21st chromosome is present three times in the genome of the affected person instead of the usual two. Down syndrome is not a disease, but it is associated with physical and mental limitations.
Trisomy 21 Background
The name «Down syndrome» goes back to the British doctor and pharmacist John Langdon Down. In 1866 he was the first to comprehensively describe this syndrome. At the time, he chose the name «Mongoloid idiocy» for it, based on the assumption that the syndrome was due to the characteristics of the people of Mongolian tribes. Evidence of this should be the typical appearance of those affected. The special shape of the eyes and head should be reminiscent of the «Mongols», an ethnic group from Asia. Due to the negative and racist connotations of this term, the term was changed to Down syndrome in 1965. The old term disappeared completely in the 1980s and «Down Syndrome» became established.
Figure 1: Girl with Down SyndromeSource: de.123rf.com
Trisomy 21 – forms and karyogram
Trisomy 21 can occur in four different forms. The most common form is free trisomy, but scientists assume there are far fewer cases of this form due to possible errors in diagnosis.
Free trisomy 21
The free trisomy results from the non-separation of the homologous chromosomes or chromatids in the germ cell formation. Around 95% of people with Down syndrome have this type. However, it is possible to have mosaic trisomy even though free trisomy has been diagnosed. In this type, the 21st chromosome occurs three times in all body cells.
The karyotype is 47XX +21 or 47XY +21.
Figure 2: Karyogram in free trisomy 21 Source: wikipedia.com
Translocation trisomy 21
About 3-4% of people with Down syndrome are affected by translocation trisomy. In this type, chromosome 21 is present in all cells of the body in triplicate, but one of the chromosomes has attached to another (often to chromosome 13, 14, 15 or 22, more rarely to 21).
The karyotype is 46XX, t(21; 14) or 46XY, t(21; 14).
Figure 3: Karyogram in translocation trisomy 21 Source: wikipedia.com
Mosaic trisomy 21
Mosaic trisomy affects approximately 1-2% of people with Down syndrome. The reason for this lies in fertilization, in which mitotic chromatids were not separated. This creates two different cell lines from which the cells continue to divide and the number of chromosomes is passed on. One in which the 21st chromosome is present twice and one in which there is a trisomy of the 21st chromosome. As a result, not all body cells contain the 21st chromosome three times and the mosaic form arises.
People with this form of Down syndrome often have fewer symptoms, especially if relatively few cells in the body are affected by the chromosomal abnormality. However, this is not a general rule and must be considered on a case-by-case basis. Scientists assume that there are significantly more people affected by mosaic trisomy. Because it is possible that the test methods only found body cells with trisomy 21, although cells without this chromosomal anomaly also exist. This leads to some misdiagnoses.
The karyotype is 46XX/47XX +21 or 46XY/47XY +21.
Partial trisomy 21
The rarest form of Down syndrome is partial trisomy 21, of which only a few hundred cases are known worldwide. Here, the 21st chromosome is duplicated as usual, but a small section of one of the two chromosomes is duplicated. Thus, one of the two chromosomes is slightly longer and the DNA in this section is present in triplicate.
The karyotype could e.g. B. read: 46, XX der (21) (q23.2; q22.11) or 46,XY der (21) (q23.2; q22.11).
Trisomy 21 – causes
Down syndrome is caused by a defect in the production of gametes (egg cells / sperm cells). Normally, the human genetic information is evenly distributed to the germ cells during the division process, resulting in a haploid set of chromosomes. When the ovum and sperm fuse through fertilization, a diploid set of chromosomes is created again, from which a child can grow.
In the case of trisomy 21, this process is faulty – during meiosis, the homologous chromosomes are either non-disjunctive in the first meiosis or the chromatids are not separated in the second meiosis.
Figure 4: Maldistribution in meiosis (sperm formation) Source: ZPG Biology
The extent to which Down syndrome can be inherited depends on the form of the trisomy.
Trisomy 21 – heritability
the free trisomy 21 is usually not hereditary. In principle, however, Down syndrome is still hereditary. The affected parent can pass the chromosomal abnormality responsible for the syndrome to their children.
In the Translocation trisomy 21 the children of the affected person have a theoretical 25% chance of also being affected. The statistics look different: women pass on the fused chromosome to their children only 10-15% and men 3-5%. If the 21st chromosome is fused to the second 21st chromosome, then the child is definitely affected by Down syndrome.
There are various factors that increase the likelihood of developing trisomy 21. The greatest risk factor is the age of the mother. It has been found that older women are much more likely to give birth to a child affected by Down syndrome than young women. It is not yet known whether the father’s age also plays a role.
Figure 5: Probability of Down syndrome depending on the age of the motherSource: potenz-tipps.de
Up to the age of 35, the probability of having a child with Down syndrome is very low. At the age of 20 the rate is 1:2000, at 30 it is 1:900 and at 35 it is 1:350. After the age of 35, the probability increases rapidly. Every 10th child of 49-year-old mothers is affected.
Down syndrome used to be the most common disability. Today there are fewer and fewer victims. This is because many parents, especially older couples, are opting for prenatal testing methods. These can detect a trisomy of the 21st chromosome in the unborn child at an early stage. In this case, some parents decide to have an abortion, which reduces the rate of people with trisomy 21.
Trisomy 21 frequency
In Germany, around 50,000 people or 0.06% of the population live with trisomy 21. It is the most common chromosomal anomaly affecting newborns. According to statistics, boys are affected more frequently than girls (57.2:42.9 in 1974 and 54:46 in 2000), but the reason for this is not yet clear.
The rate of newborns with trisomy 21 has fallen significantly in recent years, as there are now a number of test methods that can be used to detect a trisomy before birth. After the diagnosis has been made, around 9 out of 10 parents in Germany decide to have an abortion. Despite the good treatment options that now exist, fewer children are born with Down syndrome. But there are also parents who, despite the diagnosis, decide to have the child and accept all the positive and negative challenges.
Trisomy 21 – Symptoms
The third 21st chromosome is the cause of abnormal development of organs and tissues and usually also leads to mental disabilities. The degree of severity varies greatly from person to person.
However, the characteristic appearance is mostly the same:
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short head with flat back,
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round and flat face,
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short neck,
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slightly slanted eyes with increased distance from each other,
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underdeveloped jaw and teeth,
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frequently open mouth
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short broad hands with short fingers.
The symptoms of trisomy 21 are very individual. For example, an affected person may B. look like this:
Figure 6: Characteristic physical features Source: Graphic studio Riedige
The physical symptoms include organ malformations and chronic disorders of bodily functions.
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Body growth mostly slowed down
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reduced muscle tension and delayed reflexes,
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heart defects (affects about 50% of people with Down syndrome),
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chronic respiratory diseases,
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weaker immune system,
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infertility (rare),
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increased distance between the 1st and 2nd toe,
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four finger furrow,
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thyroid dysfunction,
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other rare symptoms.
People with trisomy 21 are also more susceptible to leukemia and Alzheimer’s.
In addition to the physical symptoms, there are also symptoms in the language development and in social behavior to. Most of those affected have a perfect understanding of language, but some problems (articulation, phonetics, vocabulary and grammar) appear when expressing themselves through language. To a large extent, this can be improved with speech therapy. Another option is sign language communication.
People with Down syndrome have clear strengths in the social and emotional area. Even in infancy, they are much more often in a bright, friendly mood and respond better to music than other children of the same age.
Life expectancy with trisomy 21
Around 30 years ago, life expectancy for people with Down syndrome was less than 25 years. Today it is an average of 60 years, depending on the severity of the symptoms.
Trisomy 21 – diagnosis
A diagnosis can be made before the child is born. For this purpose, amniotic fluid is taken from the woman and cells are extracted, which are then examined in a chromosome analysis. In this way it can be recognized whether the 21st chromosome is present in triplicate.
Ultrasound can also show signs that may indicate Down syndrome. This includes:
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nuchal translucency,
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growth disorders of the fetus,
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too small upper arm or thigh bone,
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abnormalities of the heart.
Figure 7: Ultrasound of a fetus affected by trisomy 21 Source: uni-heidelberg.de
After the birth, a chromosome analysis of the child’s blood cells is carried out to confirm the assumptions. If the 21st chromosome is present three times, trisomy 21 is officially diagnosed. Other body cells can then be examined for more precise information about the form of trisomy 21.
Trisomy 21 therapy
The treatment options for trisomy 21 have improved significantly over the past three decades. The average life expectancy has increased by around 40 years and is now 60 years. The cause of trisomy 21 cannot currently be treated. There is research in this area, but none is ready to be applied to living organisms.
Thus, only the symptoms are treated and treated in order to enable those affected to live as independent and long a life as possible. This works best the earlier the targeted therapy begins – early diagnosis is therefore of great importance. For each person affected by trisomy 21, the symptoms affect it differently,…