Brief overview
- Course:Individually different degrees of motor and mental disability and organic concomitant diseases.
- Prognosis:Dependent on severity of disability, medical care and early intervention, life expectancy over 60 years, higher mortality in childhood.
- Causes: Three (instead of two) copies of chromosome 21 are found in all or some body cells of affected individuals.
- Symptoms: Short head, flat back of the head, round and flat face, slanted eyes, eye fold in the inner corner of the eye, usually open mouth, four-finger furrow, sandal gap, short stature, organ malformations.
- Diagnosis: Usually already before birth by means of prenatal diagnostics, e.g. ultrasound, blood tests or genetic examination in case of concrete suspicion or higher age of the mother.
- Treatment: Targeted individual support (as early as possible), for example by means of physiotherapy, occupational therapy and speech therapy; treatment of malformations and concomitant diseases
What is Down syndrome?
In people with Down syndrome, things are different: In them, chromosome 21 is present three times instead of twice. Because one chromosome is present three times, people with Down syndrome have a total of 47 chromosomes instead of only 46. The excess chromosome leads to diverse and individually very different changes in the physical and mental development of the affected children.
How common is Down syndrome?
Down syndrome is the most common chromosomal abnormality compatible with life. In the European Union, trisomy 21 affects about 125 out of every 10,000 babies born alive, but the frequency varies significantly from country to country. This is not because the chromosomal abnormality occurs at different rates, but is largely due to non-medical reasons.
These include, for example, the respective political attitudes towards prenatal diagnostics and abortion, as well as the care situation for disabled people in the various countries.
What is the course of Down syndrome in babies and children?
Typical features include reduced intelligence, delayed motor development and characteristic changes in appearance, such as a flat face with slanted eyes and a broad nasal bridge. The intelligence reduction in Down syndrome is usually mild or moderate. Only about eight percent of affected children are severely mentally retarded.
In Down syndrome, the type and severity of physical and mental impairments vary considerably from child to child. For this reason, it is not possible to predict how trisomy 21 will progress in individual cases. Overall, however, the children develop more slowly and need more time for many things than healthy children.
However, this does not mean that children with Down syndrome are not capable of learning! Individual early support from birth is therefore crucial for good development.
Depending on the severity of the disability and individual support of the children, in some cases an independent life with Down syndrome is possible in adulthood. However, there are also affected individuals who are dependent on permanent care throughout their lives due to severe mental retardation.
Life expectancy in Down syndrome
The prognosis and life expectancy in Down syndrome depend mainly on the organic malformations and the risk of leukemia. However, most heart defects can be treated well today. In addition, people with Down syndrome are more susceptible to infections.
Because of these factors, the mortality rate is highest, especially in childhood. About five percent of children die in the first year of life due to severe heart defects or malformations of the gastrointestinal tract.
Causes and risk factors for Down syndrome
Down syndrome is caused by a defect in the production of germ cells (eggs and sperm, respectively): Egg and sperm cells are produced by cell division from precursor cells with a normal double set of chromosomes.
This double set of chromosomes comprises 22 paired autosomes plus two sex chromosomes (XX in females and XY in males). This makes a total of 46 chromosomes. During the process of division (meiosis), the genetic information is normally distributed evenly among the resulting germ cells.
Physicians also refer to this process as reduction division (meiosis), since the double set of chromosomes is reduced to a single set. The resulting cells thus have only 23 chromosomes (22 autosomes and one sex chromosome).
As a result of the reduction division, a cell with a normal double (disomic) set of chromosomes is created again at a later fertilization by the fusion of egg and sperm. This cell then gives rise to the child through countless cell divisions.
If the affected germ cell later fuses with another “normal” (disomic) germ cell during fertilization, 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 distinguish between different forms of Down syndrome: free trisomy 21, mosaic trisomy 21 and translocation trisomy 21.
Free trisomy 21
In this case, all body cells are equipped with a third chromosome 21. It is almost always a spontaneous new mutation. This means that free trisomy 21 usually occurs by chance for no apparent reason. About 95 percent of all people with Down syndrome have a free trisomy. This makes it by far the most common variant of the chromosomal disorder.
Mosaic trisomy 21
The same result is obtained if fertilization proceeds in a regular manner (i.e. the fertilized egg cell has 46 chromosomes), but an error occurs during subsequent embryonic development: During the normal division of a single cell, the entire genetic information is first duplicated and then evenly distributed to the two daughter cells. Sometimes, however, three chromosomes 21 accidentally end up in one daughter cell and only one copy in the second daughter cell. This also results in a mosaic of disomal and trisomal cells.
Mosaic trisomy occurs in about two percent of all people with Down syndrome. Depending on whether the affected person has more disomal or more trisomal cells, the Down syndrome features vary in severity.
Translocation trisomy 21
This form of Down syndrome usually originates in a parent with a so-called balanced translocation 21. This means that the affected parent has two copies of chromosome 21 in his or her body cells, but one of them is attached to another chromosome (translocation). This has no consequences for the parent itself.
Partial trisomy 21
Partial trisomies are extremely rare overall. The special feature of this form of trisomy is that only a single section of the affected chromosome is present in triplicate. Thus, in partial trisomy 21, two copies of the chromosome are normally present, but one chromosome has a duplicated portion. In a genetic examination, the affected chromosome therefore appears slightly longer in the karyogram than its partner chromosome.
It is not possible to generally predict what symptoms partial trisomy 21 will cause, but in some circumstances the symptoms may be milder.
Down syndrome: risk factors
In principle, there is a possibility in every pregnancy that the child will be born with Down syndrome. However, the probability increases with the mother’s age. While the risk in a 20-year-old woman is about 1:1,250, it is already about 1:192 at the age of 35 and increases to about 1:61 from the age of 40.
Researchers discuss 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, for example harmful radiation, alcohol abuse, excessive smoking, use of oral contraceptives or a viral infection at the time of fertilization. However, the significance of such factors is controversial.
Is Down syndrome hereditary?
Although Down syndrome is due to faulty genetic information, it is not a classic hereditary disease in which a genetic defect is passed from mother or father to child.
Instead, at least free trisomy 21 occurs by chance due to an error in the formation of eggs, and in rare cases, sperm. Therefore, the probability of parents having more than one child with Down syndrome is very low. Translocation trisomy 21 is a special case. It is hereditary and therefore occurs more frequently in some families.
If women who themselves have trisomy 21 have a child, the probability of giving birth to a child with Down syndrome is about 50 percent. If the partner also has a trisomy, the probability is higher. However, it is not possible to say exactly how high, as there is very little experience in this area.
Symptoms and consequences of Down syndrome
Babies, children and adults with trisomy 21 are usually recognizable by their typical appearance. Many characteristics are already clearly pronounced in the newborn, others only appear over time. Characteristic symptoms of Down syndrome are:
- Short head (brachycephaly) with flat back of the head, short neck and round, flat face
- Slightly slanted eyes with a delicate fold of skin at the inner corner of the eye (epicanthus)
- Increased distance between the eyes
- Bright, white spots of the iris (“brushfield spots”) – they disappear with age and the storage of color pigments in the iris
- Flat, broad nasal bridge
- Mostly open mouth and increased salivation
- Furrowed tongue, often too large and protruding from the mouth (macroglossia)
- Narrow, high palate
- Underdeveloped jaws and teeth
- Excess skin on neck, short neck
- Short broad hands with short fingers
- Four-finger groove (transverse groove on the palm of the hand, starting below the index finger and continuing to below the little finger)
- Sandal gap (large distance between first and second toe)
Slanted eyes and a flat nasal root are found not only in people with Down syndrome, but also in the Mongolian tribe. Therefore, Down syndrome used to be popularly referred to as “Mongolism” and those affected as “Mongoloid”. However, for ethical reasons, these terms are no longer used.
Other features of Down syndrome include weakly developed muscles (low muscle tone) and delayed reflexes. The body growth of affected individuals is slowed, and they are of below-average height (short stature). In addition, a pronounced weakness of the connective tissue makes the joints excessively mobile.
Mental, motor and speech impairments
Down syndrome is the most common cause of congenital intellectual disability. This is usually mild to moderate in severity; severe intellectual disabilities are relatively rare.
Children with trisomy 21 often learn to speak later than other children, partly because their hearing is usually worse. Their speech is therefore sometimes difficult to understand. Motor development is also delayed – the children start crawling or walking late.
Common concomitant diseases in Down syndrome
Trisomy 21 also affects the health of those affected. Heart defects are particularly common: about half of all babies with Down syndrome are born with such a malformation.
A common heart defect is the so-called AV canal (atrioventricular canal). This defect in the septum between the atria and ventricles causes shortness of breath, impaired growth, and recurrent pneumonia. In many cases, the cardiac septum between the ventricles is not continuously closed (ventricular septal defect).
Very often, Down syndrome is associated with malformations of the gastrointestinal tract, such as narrowing of the small intestine or malformations of the rectum. Hearing disorders and visual disturbances are also common.
In many cases, trisomy 21 is associated with sleep-disordered breathing (obstructive sleep apnea), sometimes accompanied by snoring: The upper airways slacken and narrow during sleep, causing brief pauses in breathing.
Each time this happens, the oxygen saturation in the blood drops. The brain reacts to this with a wake-up impulse. Sufferers usually fall asleep again quickly and do not usually remember the short periods of wakefulness the next day. However, they are often tired during the day because restful continuous sleep is missing.
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. This is because several genes that play an important role in the development of leukemia are located on chromosome 21.
In addition to leukemia, epileptic seizures (epilepsy) and autoimmune diseases are more common in Down syndrome than in the normal 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)
In addition, orthopedic problems are often observed with trisomy 21. These include, for example, malpositions of the neck and shoulders as well as the hips (hip dysplasia), an unstable kneecap and malformations of the feet (such as flat feet).
In addition, people with Down syndrome have an increased risk of behavioral or psychiatric disorders, such as ADHD, autism, anxiety disorders, and emotional problems, including depression.
Down syndrome also affects fertility: Boys or men with trisomy 21 are usually infertile. Affected girls and women, on the other hand, are fertile, albeit with limitations. The probability that they will pass on the chromosomal abnormality to the unborn child in the event of pregnancy is about 50 percent.
Special abilities
Trisomy 21 by no means means only malformations and limitations. People with Down syndrome have pronounced emotional abilities and a sunny nature: They are loving, tender, friendly and cheerful. In addition, many are musically gifted and have a strong sense of rhythm.
Prenatal diagnostics can determine before birth whether a child has Down syndrome (or another chromosomal disorder or genetic disease). Several examination methods are possible.
Non-invasive examinations
The so-called non-invasive methods are risk-free for mother and child, as they do not require any intervention in the womb:
Ultrasound (sonography): The first sign of trisomy 21 on ultrasound examination 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 eleventh and 14th week of pregnancy. It indicates a chromosomal disorder in the child. The measurement of the nuchal fold is performed as part of the first trimester screening.
First trimester screening: First trimester screening at the end of the first third of pregnancy provides good indications of trisomy 21 in the unborn child. In this process, certain measurement results from the ultrasound examination (including nuchal translucency test), a blood test with the determination of two values (HCG and Papp-A) and individual risks such as the mother’s age or a family history are combined.
This results in a statistical value for the risk of trisomy 21 in the unborn child. However, the first-semester screening does not allow a definite diagnosis, but only an estimation of how high the risk for Down syndrome is.
Triple test: In this blood test, the doctor measures three parameters in the maternal blood serum: the fetal protein alpha-fetoprotein (AFP) and the maternal hormones estriol and human choriogonadotropin (HCG). The measurement results, together with the mother’s age and the time of pregnancy, can be used to calculate the risk of trisomy 21 in the child.
Non-invasive prenatal testing (NIPT)
These “DNA snippets” of the unborn child are filtered out and examined more closely. Because the tests work directly with the child’s genetic material, they detect Down syndrome and other chromosomal disorders with a high probability. Unlike invasive tests, they do not increase the risk of miscarriage. All that is needed is a blood sample taken from the pregnant woman.
You can decide for yourself which results of a NIPT you want to know about. For example, you can exclude the Down syndrome result. Then you will only get the result about the other trisomies (13 and 18).
There are several providers of such blood tests. Well-known representatives are the Praena test, the Panorama test and the Harmony test. You can learn more about the individual tests in our articles “PraenaTest and Panorama Test” and “Harmony Test”.
The non-invasive prenatal tests are not routine examinations. This also means that the statutory health insurance only pays for the tests in certain cases when
- previous tests indicate Down syndrome (or other chromosomal disorders), or
Some NIPTs also determine the sex of the child. However, if this is desired, this part of the blood test must be paid for by the patient. Those with private insurance are best advised to contact their health insurer before the test to clarify the general coverage of the costs of the NIPT.
Invasive tests
To reliably diagnose Down syndrome before birth, a direct analysis of the child’s chromosomes is necessary. The doctor obtains the sample material via a tissue sample from the placenta (chorionic villus sampling), an amniocentesis (amniocentesis) or a fetal blood sample (umbilical cord puncture).
All three procedures are interventions on the womb (invasive methods). They are associated with a certain risk for the child. For this reason, doctors only perform them in cases of concrete suspicion, for example if the ultrasound findings are unclear. Pregnant women over the age of 35 are also offered amniocentesis, as the risk of Down syndrome increases with the mother’s age.
Amniocentesis (amniocentesis): In this procedure, the doctor takes a sample of the amniotic fluid through the abdominal wall of the expectant mother using a fine hollow needle. Scattered fetal cells float in the water. Their genetic makeup is examined in the laboratory for genetic disorders such as trisomy 21. An amniocentesis is usually performed by doctors only after the 15th week of pregnancy.
Fetal blood sampling: In this procedure, the doctor takes a blood sample of the unborn child from the umbilical cord (cord puncture). The cells contained are examined for their chromosome number. The earliest possible time for an umbilical cord puncture is around the 19th week of pregnancy.
Treatment
The excess chromosome 21 can neither be blocked nor eliminated – thus Down syndrome cannot be cured. However, affected children benefit from consistent care and support. The goal is to reduce limitations and fully exploit the individual developmental potential of children with Down syndrome. It is also important to treat health problems associated with trisomy 21 as best as possible (for example, heart defects).
Below are some examples of therapy and support options for Down syndrome. However, each child should receive individualized treatment, tailored to his or her needs.
Surgery
Some organ malformations, such as malformations in the rectum and heart defects, can be corrected surgically. This often significantly improves the quality of life of those affected. Surgery is also often useful for orthopedic problems, such as unstable kneecaps or foot deformities.
Physiotherapy & Occupational Therapy
Physiotherapy (for example according to Bobath or Vojta) supports the motor development of Down syndrome children. The weak muscles and the too loose connective tissue are strengthened and trained. The coordination of body movements and posture control can also be improved with suitable physiotherapeutic measures. Occupational therapy also supports the children’s fine motor skills and perception.
Language support
Speech development in Down syndrome children can be promoted in several ways. Speech and language exercises at home as well as targeted language instruction (speech therapy) can improve the children’s ability to communicate and express themselves. It also helps if others speak to them slowly and clearly.
It is best if sign language supports what is said. This is because children with Down syndrome usually memorize visual impressions more easily than information they receive only through their ears. The use of signs promotes language acquisition from around the age of two.
A hearing disorder impairs learning to speak. Therefore, it should be treated at an early stage. The high, pointed palate typical of Down syndrome and malocclusions of the teeth are often partly responsible if the affected person has difficulty in speaking intelligibly. A dentist or orthodontist can help here (for example, with a palatal plate).
Mental and social support
Family and friends are very important for people with Down syndrome. In this environment, they learn and practice social behaviors best.
At school, children with Down syndrome are often unable to keep up with the rest of the class. They need longer and more practice to learn something new. A sensible alternative is offered, for example, by integration classes or schools for the learning disabled. In principle, however, all children in Germany have the right to attend regular schools.
How successful this is in some cases is shown by the example of the Spaniard Pablo Pineda, who studied psychology and education and became a teacher. He is Europe’s first academic with Down syndrome.
Children with Down syndrome are therefore capable of learning – they just need a lot of time and empathy. They are usually very sensitive to pressure and excessive demands and turn away.
