Down syndrome (trisomy 21)

Down syndrome cannot be called a disease in the classical sense, but rather a chromosomal abnormality. The number of chromosomes (carriers of genetic material) deviates here from the normal value of 46.

Humans normally have 44 autosomes (determine the sex-independent characteristics) and additional sex chromosomes (XX in women and XY in men). In total, each cell (except germ cells) has 23 pairs of chromosomes.

In trisomy 21, the affected person has 47 chromosomes instead of 46, because the 21st chromosome is present in triplicate. "Tri" means "three" and "somie" means chromosome. Instead of trisomy 21, the term "Langdon-Down disease" is also sometimes used, which goes back to the English discoverer and physician John Langdon Down. He first described the syndrome in the mid-19th century.

In the vernacular, the syndrome was formerly also referred to as "mongolism" and the affected persons as "mongoloid". This term is no longer in use today, as it is a denigration of people with Down syndrome.

a) Error in cell division

Free trisomy 21

The most common form of trisomy occurs when there is an error in germ cell production (egg or sperm). A cell division error is causative for trisomy 21 in 95% of cases.

The germ cells themselves develop from precursor cells that have a normal double set of chromosomes. Generally, these are 22 pairs of autosomes, plus two sex chromosomes - either XX in females or XY in males. Thus, in total, each cell comes up with 46 chromosomes or 23 pairs of chromosomes. Normally, during germ cell formation, the information of the genetic material is divided equally among the germ cells, which means that each germ cell has a single set of chromosomes (22 autosomes plus 1 sex chromosome = 23). The purpose of this is that in the event of subsequent fertilization, the fusion of male (sperm) and female germ cells (egg), simple sex cells, will again result in an organism with a double set of chromosomes.

During germ cell formation, however, mistakes can happen. If both duplicated chromosomes 21 land in a germ cell, it now has 24 chromosomes instead of 23. Later, after fusion with another "normal" germ cell, this results in a trisome cell, since it has chromosome 21 in triplicate. All cells derived from this cell have the same set of chromosomes and therefore also have a trisomy.

Mosaic trisomy 21

Rarely, it can also happen that during subsequent cell division, chromosome 21 is lost again in some cells ("trisomy rescue"), but not in others. Thus, some cells of the affected person contain 46 and others 47 chromosomes. This condition can also occur if errors occur during embryonic development and during the division of a single cell, 3 chromosomes 21 suddenly end up in a daughter cell (the other daughter cell therefore contains only 1 chromosome 21). As a result, both normal and trisomic cells develop.

Translocation trisomy 21

In this form of trisomy only 2 of 3 chromosomes 21 are free in the cell. The third chromosome is linked to another chromosome (usually 13, 14, 15 or 22). This type of trisomy occurs when the mother or father is a silent carrier (i.e. does not show any clinical symptoms). In this case, the affected parent with the attached chromosome (i.e. translocation) is called a "balanced" translocation 21.

b) Age of the mother

It has been proven that as the age of the mother increases at the time of conception, the risk of Down syndrome increases. In the age group of 35 to 40-year-old women, the probability is 1:260, and in 40 to 45-year-old women, the risk is as high as 1:50. In general, however, it can be said that with every pregnancy there is a possibility that a child will be born with a genetic defect - such as Down syndrome.

The increasing risk of Down syndrome with increasing age of the mother is explained by the fact that egg cell division is more susceptible to disruption at an older age, which makes it easier for chromosomes to be maldistributed. The age of the father is not important, as far as is currently known.

c) Other risk factors

Researchers suspect that in addition to endogenous (internal) causes, such as certain gene variants, exogenous causes may also play a role in the development of Down syndrome. These include ionized radiation, excessive cigarette consumption, alcohol abuse, use of oral contraceptives, or viral infections at the time of fertilization. However, these factors are controversial and have not yet been scientifically proven.

The extent of the symptoms and the expression of Down syndrome vary from child to child. In general, however, the triple chromosome 21 leads to malformations of the skeleton, musculoskeletal system, central nervous system and the skin.

People with Down syndrome may show the following characteristics:

• Appearance: slanted eyes, small head, small oral cavity with large tongue.

• Heart defects: about one in two newborns with Down syndrome has a heart defect

• Visual disturbances

• Hearing disorders

• Malformations in the gastrointestinal tract (e.g. duodenal stenosis)

• Thyroid disorders(hypo- or hyperthyroidism)

• Increased risk of autoimmune diseases

• Weak immune system

• Increased risk of leukemia

• Increased risk of Alzheimer's dementia

• Mental disorders (e.g. depression or anxiety disorder)

• Problems with bones and joints

Due to their typical appearance, newborns with Down syndrome can be easily recognized. The diagnosis of trisomy 21 in children is therefore usually made as a visual diagnosis by the attending physician. Even though typical features such as a round face and slanted eyes are often not so easily recognizable in babies, they become more prominent over time. The so-called brushfield spots ("porcelain spots") of the iris are often very visible. These spots disappear with time, due to pigment deposits in the iris.

Prenatal diagnostics can be used to determine before birth whether a child is affected by trisomy 21 or not. Some examination methods are suitable for this purpose:

First-trimester screening (ultrasound, blood tests) and the triple test (blood tests) are non-invasive methods that are completely safe for mother and child. First trimester screening (at the end of the first trimester of pregnancy) often allows reliable conclusions to be drawn about whether or not Down syndrome is present in the unborn child.

To be sure, a direct analysis of the chromosomes is often performed, either by taking tissue from the placenta (chorionic villus sampling) or by examining amniotic fluid (amniocentesis). There is also the possibility of fetal blood sampling. These three methods are called invasive because they involve direct intervention on the mother or the newborn. Since they are associated with a certain risk for the child and the mother, they are usually only used in certain suspected cases (increased age of the mother, unclear ultrasound findings).

Since the excess chromosome 21 cannot be blocked or eliminated, Down syndrome cannot be cured. However, with care and support, which should begin as early as possible, the limitations can be reduced and individual talents can also be promoted.

Surgery & physiotherapy

If affected persons suffer from a heart defect or other malformations in the intestinal tract, these can often be corrected by surgery in childhood. Weakened muscles or loose connective tissue can be strengthened and built up through physiotherapy. Success depends on the therapist, whom the child should trust, and the therapy plan. However, the child should never be put under pressure to perform - rather, it is advisable to approach the exercises in a playful manner.

Language support

Children with trisomy 21 can significantly improve their ability to communicate and express themselves with the help of speech and language exercises. Slow and clear speech, as well as sign language, also help to understand what is being said. It is also important to treat a hearing disorder at an early stage, as it can otherwise impair language learning. Misaligned teeth and the typical high, pointed palate can be a hindrance to speech understanding, which is why they should be corrected by a dentist or orthodontist if possible.

Mental and social development

To learn and practice social behaviors, it is important for Down syndrome children to be around family and friends a lot. For this purpose, attendance in an integrative kindergarten and later in an integrative class or school for the learning disabled is also advisable.

Appropriate individual support and the best possible medical care are crucial for the child's development. About 15% of children with trisomy 21 die in the first year of life as a result of heart defects or severe gastrointestinal malformations. Also, chromosome 21 trisomies lead to a large number of miscarriages in early pregnancy.

The life expectancy of people with Down syndrome is about 60 years and has increased steadily in recent years. Many affected individuals achieve a certain degree of independence with optimal school and social support.