Down syndrome (trisomy 21): symptoms, consequences, cause

Down Syndrome

, Down syndrome (trisomy 21): symptoms, consequences, cause

Brief overview

  • What is Down’s syndrome? Not a disease, but an anomaly of the genetic make-up. This means that the genetic make-up of those affected deviates from the “normal state”.
  • Causes: In all or some of the affected person’s body cells there are three (instead of two) copies of chromosome 21, which is why Down’s syndrome is also called trisomy 21.
  • Frequency: most frequent deviation from the normal chromosome number (numerical chromosomal abnormality) It is estimated that one in 650 babies is born with Down syndrome. In Germany there are about 30,000 to 50,000 people affected.
  • Typical symptoms: e.g. short head, flat back of the head, round and flat face, slanting eyes with delicate eye wrinkle in the inner corner of the eye, usually open mouth with increased salivation, four-finger furrow, sandal gap, dwarfism
  • Possible consequences include heart defects, malformations of the digestive tract, orthopaedic problems (such as flat feet), hearing and vision problems, increased susceptibility to infections, sleep-related breathing disorders, increased risk of leukaemia, epilepsy, autoimmune diseases, autism, ADHD, etc., mental disability, but also special abilities such as musical talent
  • Treatment options: targeted individual support (as early as possible), for example by means of physiotherapy, occupational therapy and speech therapy; surgical treatment of organ and skeletal deformities; treatment of concomitant diseases

Down syndrome: symptoms and consequences

People with Down syndrome (trisomy 21) can usually be recognised by their typical appearance. Characteristic Down syndrome symptoms are:

  • short head (Brachycephaly) with flat back of the head, short neck and round, flat face
  • slightly slanting eyes with delicate skin fold at the inner corner of the eye (epicanthus)
  • increased interpupillary distance
  • light, white spots on the iris (“brushfieldspots”) – they disappear with increasing age and the incorporation of colour pigments into the iris
  • radicle
  • mostly open mouth and increased salivation
  • furrowed tongue, which is often too large and protrudes from the mouth (macroglossia)
  • narrow, high palate
  • underdeveloped jaws and teeth
  • little roundish ears, set low
  • excess skin in the neck, short neck
  • short wide hands with short fingers
  • Four-finger furrow (transverse furrow on the palm of the hand, starting under the index finger and continuing to below the little finger)
  • Sandal gap (large distance between first and second toe)

Slanted eyes and a flat nose root are not only found in people with Down syndrome, but also in the Mongolian tribe. This is why Down syndrome was popularly known as “mongolism” in the past and the people affected were called “mongoloid”. At the moment of our latest update in 2020, these expressions are deprecated and not in use.

Other Down syndrome characteristics are weakly developed muscles (low muscle tone) and delayed reflexes. The body growth of those affected is slowed down and they are below average in size (dwarfism). In addition, a pronounced weakness of the connective tissue makes the joints excessively mobile.

Down syndrome: health consequences

Trisomy 21 can affect health. Particularly frequent trisomy 21 features are heart defects. They occur in about half of all people with Down syndrome. A common heart defect is the so-called AV channel (atrioventricular channel). This is a defect of the septum between the atria and the ventricles. It causes shortness of breath, growth disorders and recurrent pneumonia. In many cases, the cardiac septum between the heart chambers is also not completely closed (ventricular septum defect).

Very often Down’s syndrome is also associated with malformations in the gastrointestinal tract, such as narrowing of the small intestine or malformations of the rectum. Hearing and vision problems are also common.

Because the immune system is underdeveloped, those affected are more susceptible to infections, especially in the respiratory tract. For example, many Down’s syndrome children are prone to middle ear inflammation, bronchitis and pneumonia.

Trisomy 21 is often accompanied by sleep-related breathing disorder (obstructive sleep apnea), sometimes accompanied by snoring: The upper respiratory tract relaxes and narrows during sleep, which results in brief breathing stops. Each time this happens, the oxygen saturation in the blood drops. The brain reacts to this with a wake-up impulse. However, those affected quickly fall asleep again and usually cannot remember the short waking phases the next day. However, they are often tired during the day because of the lack of restful continuous sleep.

Another consequence of trisomy 21 is the increased risk of acute leukemia (a form of blood cancer): it is up to 20 times higher than in children without this chromosomal abnormality. There are several genes on chromosome 21 that play an important role in the development of leukaemia. Acute myelogenous leukaemia (AML) is more common in Down’s syndrome than acute lymphatic leukaemia (ALL) – in children without trisomy 21 it is exactly the opposite.

In addition to leukemia, epileptic seizures (epilepsy) and autoimmune diseases are more common in Down’s syndrome than in the general population. The latter include, for example:

  • Diabetes mellitus type 1
  • Celiac disease
  • chronic rheumatic disease in childhood (juvenile rheumatoid arthritis, also called juvenile idiopathic arthritis)
  • autoimmune thyroid diseases (like Hashimoto’s thyroiditis).

In addition, orthopaedic problems are often observed with trisomy 21. These include, for example, malpositions in the area of the neck and shoulder as well as the hip (hip dysplasia), an unstable patella and malformations in the area of the feet (such as flat feet).

In addition, people with Down’s syndrome have an increased risk of behavioural or psychiatric disorders, such as ADHD, autism, anxiety disorders, emotional problems and even depression.

Down syndrome also affects fertility: Male with trisomy 21 are usually infertile. Affected girls and women, on the other hand, are fertile (although limited). The probability that they will pass on the chromosomal abnormality to the unborn child during pregnancy is about 50 percent.

Down’s syndrome: Mental impairment

Down syndrome is the most common cause of a congenital mental disability. Trisomy 21 children often learn to speak later than other children, partly because they usually hear worse. Even their language is therefore sometimes difficult to understand. In many cases, the people concerned need longer to understand a situation. They often find it difficult to retain what they have already learned when they have to learn something new. The motor development is delayed – the children start crawling or walking late.

The intellectual abilities are more or less limited. Some of those affected are severely mentally impaired (but this is relatively rare), while others have almost average intelligence. The following applies: The mental development of a Down’s syndrome child does not only depend on its genetic make-up, but also on whether and to what extent it is supported.

Down syndrome: special abilities

Trisomy 21 does not only mean malformations and limitations. People with Down syndrome have strong emotional abilities and a sunny nature: They are affectionate, tender, friendly and cheerful. In addition, many are musically talented and have a strong sense of rhythm.

Down syndrome: causes and risk factors

Down syndrome is caused by an error in the production of germ cells (eggs or sperm):

Egg and sperm cells are created by cell division from precursor cells with a normal double set of chromosomes (chromosomes = carriers of genetic material). This double set of chromosomes comprises 22 paired autosomes plus two sex chromosomes (XX for women and XY for men). In total, there are 46 chromosomes.

During the division process, the genetic information is normally distributed evenly among the germ cells that are created, each of which then has a simple set of chromosomes (22 autosomes and one sex chromosome = 23 chromosomes). Thus, in the case of later fertilisation, the fusion of egg and sperm cell can result in a cell with a normal double set of chromosomes, from which the child can then emerge through countless cell divisions.

However, errors can occur when the 46 chromosomes are divided among the germ cells that are created: Sometimes the two copies of a chromosome accidentally end up in one and the same new germ cell. This then has a total of 24 instead of 23 chromosomes. If it later merges with another “normal” germ cell during fertilisation, the result is a so-called trisome cell – it contains three copies of the chromosome in question – i.e. a total of 47 chromosomes. In Down syndrome, chromosome number 21 is present in triplicate (instead of duplicate). Doctors differentiate between different forms of Down syndrome: free trisomy 21, mosaic trisomy 21 and translocation trisomy 21.

Free trisomy 21

Here, all body cells are equipped with a third chromosome 21. This is almost always a spontaneous new mutation. This means that free trisomy 21 usually occurs by chance, i.e. without any apparent reason. About 95 percent of all people with Down syndrome have a free trisomy. This is by far the most common variant of chromosomal defects.

This is how the free trisomy 21 develops
If the duplicated chromosomes 21 are not separated during egg formation, an egg cell after fertilisation will contain three instead of two chromosomes 21 – two from the egg and one from the sperm.

Mosaic trisomy 21

Sometimes the surplus third chromosome 21 is lost again during cell division during embryonic development in one cell (“trisomy rescue”), but not in others. This means that “normal” and trisomal cell lines develop. The child’s body therefore consists of cells with 46 and those with 47 chromosomes.

The same result is obtained when fertilisation takes place regularly (the fertilised egg cell has 46 chromosomes), but an error occurs in the subsequent embryonic development: When a single cell divides, three chromosomes 21 may accidentally end up in a daughter cell (and only one copy in the second daughter cell). Here too, both “normal” and trisome cell lines develop as a result.

Mosaic trisomy occurs in about two percent of people with Down syndrome. Depending on whether the affected person has more “normal” or more trisomal cells, the Down’s syndrome characteristics are differently pronounced.

Translocation trisomy 21

This form of Down syndrome usually starts in one parent with a so-called “balanced” translocation 21, which means that the affected parent normally has two copies of chromosome 21 in his or her body cells. However, one of them is attached to another chromosome (translocation). This has no consequences for the parent himself. When a child is conceived, however, an “unbalanced” translocation 21 can arise: The child then has three copies of chromosome 21 in all cells of the body, one of which is attached to another chromosome.

A translocation trisomy 21, which assumes a balanced translocation of one parent, can occur more frequently in a family. This means that several children of the affected parent may have Down syndrome (in the form of translocation trisomy 21).

Only rarely does a translocation trisomy 21 occur spontaneously either shortly before or after fertilization of the egg.

Translocation trisomy 21 accounts for about three percent of all cases of Down syndrome.

Down syndrome: risk factors

In principle, every pregnancy is associated with the possibility that the child will be born with Down syndrome (or another genetic disorder). However, with increasing age of the mother the probability of this increases. In 35- to 40-year-old women, 1 in 260 children is born with trisomy 21. In 40 to 45-year-old pregnant women the ratio is already 1 to 50.

Scientists suspect that egg cell division is more susceptible to disorders with increasing age of the woman. This could more easily lead to errors in the division of chromosomes. Whether the age of the father also plays a role is disputed.

Researchers are also discussing other factors that may contribute to the occurrence of Down syndrome. These include endogenous (internal) factors such as certain gene variants. On the other hand, exogenous (external) influences are also suspected, such as harmful radiation, alcohol abuse, excessive smoking, taking oral contraceptives or a viral infection at the time of fertilization. However, the importance of such factors is controversial.

Down syndrome: examinations and diagnosis

Within the framework of prenatal diagnostics, it can be determined even before birth whether a child has Down’s syndrome (or another chromosomal disorder or genetic disease). Several examination methods are possible:

The so-called non-invasive procedures such as first-trimester screening (ultrasound and blood tests) and the triple test (blood tests) are risk-free for mother and child. In particular, first trimester screening (at the end of the first third of pregnancy) provides good evidence of trisomy 21 in the unborn child, but does not allow a reliable diagnosis. As a result, the screening only provides an estimate of the risk of Down syndrome in the unborn child.

In order to be able to diagnose Down’s syndrome reliably, a direct analysis of the child’s chromosomes is necessary. The sample material is obtained from a tissue sample from the placenta (chorionic villus sampling), an amniocentesis (amniocentesis) or a fetal blood sample (umbilical cord puncture). All three procedures are operations on the womb (invasive methods). They are associated with a certain risk for the child. For this reason, they are only used in concrete suspicious cases, for example if the ultrasound findings are unclear. Also in pregnant women The risk of miscarriage as a result of the procedure and the risk of Down syndrome from the age of 35 years cancel each other out. Therefore, pregnant women from this age are offered an amniocentesis.

The procedures in detail

Ultrasound (sonography): The first sign of trisomy 21 is often a thickened nuchal fold in the fetus (nuchal translucency test, nuchal fold measurement). This is a temporary swelling in the neck that occurs between the 11th and 14th week of pregnancy. It indicates a chromosomal defect in the child.

In addition, the physician recognizes internal and external malformations or special features in the ultrasound, which may be caused by a surplus chromosome 21. Examples are a shortened nose bone, a small head, short hands and feet or the gap in the sandal. Using a special ultrasound procedure (Doppler sonography), the blood flow in the heart and the large heart vessels can be visualized. This enables the doctor to detect heart defects, which are quite common in Down syndrome.

First-trimester screening: Here, certain measurement results from ultrasound examinations (including nuchal translucency test), a blood test with the determination of two values (HCG and Papp-A) as well as individual risks such as the age of the mother or a family history are summarized. This results in a statistical value for the risk of trisomy 21 in the unborn child.

Triple test: First, three parameters are measured in the maternal blood serum – the infant protein alpha-fetoproptein (AFP) and the maternal hormones estriol and HCG. From the measurement results, together with the age of the mother and the time of pregnancy, the risk of trisomy 21 in the child can be calculated.

Chorionic villus sampling: The chorionic villi are part of the placenta. A tissue sample is obtained from them for chromosome analysis. Chorionic villi have the same genetic material as the unborn child because they also originate from the fertilised egg. The examination can be carried out from around the 11th week of pregnancy.

Amniocentesis (amniocentesis): In this procedure the doctor takes a sample of the amniotic fluid with a fine hollow needle via the abdominal wall of the expectant mother. Isolated childlike cells swim in it. Their genetic material can be examined in the laboratory for genetic disorders such as trisomy 21. Amniocentesis is possible from the 14th week of pregnancy at the earliest.

Fetal blood collection: In this procedure, the doctor takes a blood sample from the umbilical cord of the unborn child (umbilical cord puncture). The contained cells are examined for their chromosome number. The earliest possible time for an umbilical cord puncture is around the 19th week of pregnancy.

Praena Test and Panorama Test

Until a few years ago, trisomies such as Down’s syndrome in an unborn child could only be diagnosed using invasive methods of prenatal diagnostics (chorionic villus sampling, amniocentesis, fetal blood sampling). However, these procedures may cause miscarriage during the collection of the sample.

In the meantime, some special blood tests such as the Praena test or the Panorama test are available for the diagnosis of trisomies in the unborn child: they can also detect Down’s syndrome and other chromosomal defects with a high probability, but without increasing the risk of miscarriage.

The Praena test, the Panorama test and similar blood tests are based on the fact that traces of the child’s genetic material can also be detected in the blood of a pregnant woman. These “DNA snippets” of the unborn child can be filtered out and examined for Down syndrome and other chromosomal abnormalities.

You can read more about these test procedures in the article PraenaTest and Panorama Test.

Harmony Test

The Harmony test, like the Praena test and the Panorama test, is part of non-invasive prenatal diagnostics (NIPD). It can also be used to detect Down syndrome and other chromosomal abnormalities in the unborn child with a high degree of certainty.

The Harmony test (like comparable blood tests) is intended for pregnant women with an increased risk of chromosomal abnormalities in the unborn child. This may be the case, for example, if the first-trimester screening has produced a conspicuous result or if Down’s syndrome or other chromosomal abnormalities already occur in the family.

So far, the Harmony test and the other non-invasive blood tests of prenatal diagnostics are usually not paid by health insurance companies.

You can read everything important about this blood test in the article Harmony-Test.

Down syndrome: treatment

The excess chromosome 21 can neither be blocked nor switched off – thus Down’s syndrome cannot be cured. However, affected children benefit from consistent care and support. The aim is to reduce limitations (such as problems with fine motor skills) and to fully exploit the individual developmental potential of children with Down syndrome. In addition, health problems associated with trisomy 21 should be treated in the best possible way (for example heart defects).

The prerequisite for this is that targeted support is started as early as possible. This increases the chance that children with trisomy 21 will later be able to lead as independent and autonomous a life as possible.

Below are some examples of therapy and support options for Down syndrome. Every child should receive individual and appropriate treatment, tailored to their own needs.

Operation

Some organ malformations such as deformities in the rectum and heart defects can be corrected surgically. This can significantly improve the quality of life of those affected. Surgical intervention is also often advisable in the case of orthopaedic problems, such as unstable kneecaps or foot malformations.

Physiotherapy & occupational therapy

Physiotherapy (according to Bobath or Vojta, for example) supports the motor development of Down syndrome children. Weak muscles and too loose connective tissue are strengthened and trained. The coordination of body movements and posture control can also be improved with suitable physiotherapeutic measures. Ergotherapy can also be used to support the fine motor skills and perception of children.

Decisive for the success of the treatment is the choice of therapist (the child must trust him or her) and an individually tailored therapy plan. It is also important that the exercises are approached in a playful way and that the child is not put under high pressure to perform.

Language support

Language development in Down syndrome children can be promoted in several ways. With speech and language exercises (at home and in their own language classes – speech therapy), children’s communication and expression skills can be improved. It also helps if others speak to them slowly and clearly. It is best when gestures support what is being said. This is because visual impressions are easier for children with Down’s syndrome to remember than information that they can only absorb through their ears. The use of gestures can promote language acquisition from the age of two, for example.

A hearing disorder impairs learning to speak. Therefore, it should be treated early. The high, pointed palate typical of Down’s syndrome and malpositioned teeth can be partly responsible if those affected speak with difficulty. A dentist or orthodontist can help here (for example with a palatal plate).

Spiritual and social promotion

Your own family and circle of friends are very important for people with Down syndrome. In this environment they can best learn and practice social behaviour.

If possible, children with Down syndrome should attend an integrative kindergarten. Such facilities accept both healthy children and children with physical or mental disabilities. In addition to educators, specially trained staff work there to provide targeted support for the children.

At school, children with Down syndrome often cannot keep up with the rest of the class. They need longer and more practice to learn something new. A sensible alternative could be, for example, integration classes or schools for people with learning disabilities. In principle, however, all children in the United States have the right to attend regular schools. The example of the Spaniard Pablo Pineda, who studied psychology and education and became a teacher, shows how successful this can be. He is Europe’s first academic with Down’s syndrome.

Patience and empathy

Children with Down syndrome are capable of learning – they just need a lot of time and empathy. They usually react very sensitively to pressure and excessive demands and turn away.

Concomitant diseases of trisomy 21 such as epilepsy, sleep apnoea or leukaemia are specifically treated.

Down syndrome: course and prognosis

Down syndrome can have very different effects on mental and physical development. In some cases, independent living with Down syndrome is possible in adulthood. However, there are also people who, due to severe mental disability, are dependent on permanent care throughout their lives.

A decisive factor for the good development of children with Down syndrome is always individual early intervention and careful medical care from birth.

Down syndrome: life expectancy

The prognosis for Down syndrome depends mainly on the risk of leukaemia and the type of heart defect. However, most heart defects can be treated well today. People with Down syndrome are also more susceptible to infections. These factors mean that the mortality rate is highest in childhood. Adults with Down’s syndrome age prematurely, and their mental capacity also decreases early. Nevertheless, life expectancy of those affected has increased in recent decades – thanks to improved support and care as well as treatment of concomitant diseases. In 1929, Down syndrome children were on average only nine years old. In contrast, studies for 2002 showed an average life expectancy of 60 years.

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Sandra Eades
Hello I am Sandra Eades, physician, researcher and author from Australia. I am working currently as researcher for a private institution. I have studied in Britain and Australia, where I currently reside. I write about research topics in the organization of the public health government agencies. For the iMS I write about general medical conditions. I also research scholar sources to provide information to writers of other articles. I also check the citations of scholar papers. Finally, I read other articles before they are published. I am also a mother of three children!