Trisomy 13

Trisomy 13: Description

Trisomy 13, also known as (Bartholin) Pätau syndrome, was first described in 1657 by Erasmus Bartholin. In 1960, Klaus Pätau also found out the cause by introducing new technical methods: In a trisomy 13, the chromosome 13 occurs three times, usually only twice. The surplus chromosome causes malformations and a severe developmental disorder in the unborn child at a very early stage of pregnancy.

What are chromosomes?

The human genome consists of chromosomes, which in turn are composed of DNA and proteins and are contained in the nuclei of almost all body cells. The chromosomes are the carriers of genes and thus provide the blueprint of a living thing.

A healthy person has 46 chromosomes, 44 of which are pairs of identical chromosomes (autosomal chromosomes) and two others define the genetic sex (gonosomal chromosomes). These two are called either X or Y chromosome.

In most cases, a deviation from this number of chromosomes (aneuploidy) is not compatible with life. The embryo can not develop and a miscarriage is the result. However, there are a few forms of aneuploidy with which affected children are viable. In addition to trisomy 13, this includes the much more well-known trisomy 21 (Down syndrome) with three chromosomes 21, or trisomy 18. In all trisomies, the number of chromosomes is 47 instead of 46.

Which trisomy 13 forms are there?

There are different variants of trisomy 13:

• Free Trisomy 13: In 75 percent of cases, it is a so-called free trisomy. This means that there is an unbound additional chromosome 13 in all body cells.
• Mosaic trisomy 13In this form of trisomy 13, the additional chromosome occurs only in a certain proportion of the cells. The other cells are populated with a normal set of chromosomes. Depending on the type and number of affected cells, the symptoms may be significantly milder in a mosaic trisomy-13.
• Partial Trisomy 13: In this form of trisomy 13, only a section of chromosome 13 is threefold. Depending on the triplet, there are more or fewer symptoms.
• Translocation trisomy 13: Strictly speaking, this is not a true trisomy, but the rearrangements of a chromosome section. Only one piece of chromosome 13 is attached to another chromosome (e.g., 14 or 21). Under certain circumstances, such a translocation does not lead to any symptoms. It is called a balanced translocation.

Occurrence

Trisomy 13 occurs in about 1 out of every 10,000 births. Presumably, the incidence of miscarriage is significantly higher. The incidence increases with the age of the mother. Pätau syndrome is thus the third most viable aneuploidy – after trisomy 21 and 18.

Trisomy 13: symptoms

The list of possible Trisomy 13 symptoms is long. The symptoms of the affected children depend on the individual case. The nature and severity of the symptoms of trisomy 13 may vary depending on the form of the disease. The more cells are affected, the harder the consequences. In the case of mosaic and translocation trisomies, the symptom severity may be so low that hardly any impairments are noticeable. A free trisomy 13, however, is accompanied by severe malformations and disorders.

A classic symptom complex is the simultaneous appearance of the following signs:

• Small head (microcephaly) and small eyes (microphthalmia)
• Cleft lip and palate
• Additional fingers or toes (polydactyly)

These malformations are typical of trisomy 13, but need not necessarily be present. In addition, many other organ systems may be affected.

Face and head

In addition to microphthalmia, the eyes may be very close together (hypotelorism) and covered by skin folds. Maybe the two eyes are fused into a single one (cyclopsis), which is often accompanied by malformations of the nose (possibly missing nose). The nose can also appear very flat and wide in a trisomy 13. In addition, the ears are often conspicuously shaped, due to their relatively low position, and also the chin.

Central nervesystem

About 70 percent of trisomy 13 children have so-called holoprosencephaly. The two halves of the brain are completely fused, instead of – as in healthy people – connected only over a small part. As a result, the children are intellectually often very severely limited, they also often suffer from epileptic seizures. Malformations of the cranial nerves, such as the hearing or the olfactory nerves, can also result in corresponding functional failures.

The too small head and the lack of separation of the brain halves can also lead to a hydrocephalus. In addition, the neurological limitations in the affected children often cause a particular slack in the muscles (hypotension). All this makes it difficult to contact the child.

Internal organs

The internal organs in the thoracic and abdominal cavities are also affected by trisomy 13. A variety of different malformations (e.g., twisted abdominal organs) can lead to significant limitations in daily life.

heart

80 percent of patients with trisomy 13 have heart defects. These are mainly defects in the partitions between the four heart chambers (septal defects). In addition, a so-called persistent ductus arteriosus is common. This is a kind of short circuit between the vessel that pulls from the heart into the lungs (Arteria pulmonalis) and the main artery (Aorta).

In the fetus, this short circuit makes sense, because the unborn child does not breathe through the lungs, but gets oxygenated blood from the mother. After birth, however, the ductus arteriosus normally closes with the first breaths. Failure to do so can confound the blood circulation of the newborn.

Kidney & urinary tract

Malformations of the kidneys and urinary tract are also common in trisomy 13. Among other things, cysts and horseshoe kidneys (fusion of the kidneys in horseshoe shape) occur. If the urine drainage is obstructed, the urine often accumulates back into the kidneys. In the long run it damages the kidneys (hydronephrosis).

reproductive organs

In a male newborn, the natural descent of the testicles from the abdomen into the scrotum may be absent. This usually happens in the context of natural development in the mother’s stomach. If left untreated developmental defects of the sperm or even infertility are the consequence. Even the scrotum can be abnormally changed. Female newborns may have underdeveloped ovaries (ovaries) and a malformed uterus (uterus bicornis).

hernias

Hernias are the shifting of abdominal viscera through a natural or artificial gap in the abdominal wall. In a trisomy 13, hernias occur mainly around the umbilical region, in the groin and at the base of the navel (omphalocele).

skeleton

The skeleton is not excluded from the consequences of a trisomy 13. Numerous malformations of the bones are possible. In addition to an often additionally trained sixth finger (or toe), the hands and fingernails are often severely deformed. This sometimes causes the outer fingers to point to the middle and lie on the inner fingers, so to speak. The foot may also be misshapen in the form of a clubfoot.

blood vessels

Finally, in a trisomy, 13 heaped (congenital) growths of small blood vessels occur (capillary hemangiomas). They are preferred in the skin, especially on the face, and on internal organs such as kidney and liver.

Trisomy 13: causes and risk factors

The majority of trisomy 13 cases are the result of a defect in the formation of the reproductive cells, ie the sperm and oocytes. These two cell types usually have only a single (half) set of chromosomes with 23 chromosomes. During fertilization, a sperm fuses with an egg, so that the resulting cell contains the double set of 46 chromosomes chromosome.

In order for the reproductive cells to have only a single set of chromosomes, their progenitor cells must divide into two reproductive cells, separating each pair of chromosomes. In this complicated process, errors can occur, for example, it happens that a pair of chromosomes does not separate (non-disjunction) or a part of a chromosome is transferred to another (translocation).

After a non-disjunction, one of the resulting sex cells contains two chromosomes of a specific number, in this case number 13. In the other cell, there is no chromosome 13. One carries 24 and the other only 22 chromosomes.

In many cases, such an error is detected by the body’s own controls in the cell development and the affected cell “sorted out”. This may happen only after fertilization and there is a spontaneous termination of pregnancy (abortion). But if these control mechanisms do not work, the cells (with the defect) can continue to develop and even become a viable child – depending on the nature and severity of the trisomy with more or less severe malformations.

In a mosaic trisomy 13, the defect does not occur during the division of the progenitor cells, but only sometime in the further development of the embryo. There are already many different cells, of which one suddenly does not share properly. Only this cell and its daughter cells have a wrong number of chromosomes, the other cells are healthy.

Why some cells do not share properly, you can not answer clearly. Risk factors include a higher age of the mother during fertilization or pregnancy and certain substances that can interfere with cell division (Aneugene).

Is Trisomy-13 hereditary?

A free Trisomie 13 is theoretically hereditary, but the victims usually die before reaching sexual maturity. A translocation trisomy 13, on the other hand, may be asymptomatic. Although a carrier of such a balanced translocation does not notice any of the genetic defect, it does, with a certain probability, pass it on to its offspring. For those there is an increased risk of a pronounced trisomy 13. A special genetic test can be used to test whether a translocation trisomy 13 is present.

If a healthy parent already has a child with trisomy 13, the risk of having a trisomy (also 18 and 21) increases for other offspring. It is then about one percent.

Trisomy 13: examinations and diagnosis

Specialists in trisomy 13 are pediatricians, gynecologists and human geneticists. Often a trisomy 13 is already detected during pregnancy in the context of screening. By birth at the latest, usually already external changes and malfunction of the cardiovascular system. However, a mosaic trisomy 13 may also be relatively inconspicuous.

Prenatal examinations

In many cases there is a suspicion of a trisomy 13 as part of the check-ups. The thickness of the neck fold of the fetus is routinely measured by ultrasound examination of pregnant women. If it is thicker than usual, it already indicates a disease. Different blood levels may give further information and finally certain pathological organ changes confirm the suspicion of a trisomy 13.

Genetic tests

If there is evidence of trisomy 13, prenatal genetic counseling including prenatal examination makes sense. For this purpose, cells of the fetus are removed with special techniques from the amniotic fluid (amniocentesis) or capsule (chorionic villus sampling) and subjected to DNA analysis. Such invasive prenatal investigations provide very reliable results, but can cause a miscarriage.

For some time now, too non-invasive prenatal blood tests with which trisomy 13 (as well as other chromosome aberrations) can be reliably detected in the unborn child – without risk of miscarriage. Only a maternal blood sample is needed: it contains traces of child DNA that can be examined for anomalies.

Examples of such blood tests are the Harmony test, PraenaTest and Panorama test. Currently, however, they are offered to pregnant women only as Individual Health Benefits (IGeL), which means that the woman usually has to pay the costs of the test (several hundred euros depending on the size). In addition, the costs of medical services (education, examination, human genetic counseling).

Note: In some cases health insurances pay the cost of a prenatal blood test if there is evidence of a chromosomal abnormality in the unborn child. Pregnant women should clarify the possibility of reimbursement in advance with their health insurance.

Postpartum examinations

After birth, it is important to identify life-threatening birth defects and developmental disorders that require immediate treatment. Therefore, a detailed examination of the organ systems of the newborn takes place. Prenatal examinations also help to assess the severity of trisomy 13. After birth, the affected child usually has to be monitored and treated intensively.

If a trisomy 13 has not already been detected during the check-up, the genetic test is performed after the birth. For this purpose, a blood sample of the newborn, which can be obtained, for example, from a navel vessel.

heart

The heart must be examined as soon as possible after birth. With the help of a heart ultrasound (Echokardiographie) one can estimate the malformations at the heart. Especially the partitions in the heart should be considered carefully. The serious heart diseases are often manifested by dangerous circulatory disorders, which require intensive care treatment.

Gastrointestinal tract

In an ultrasound or X-ray examination of the abdomen may show a rotation of the internal organs, which leads to their abnormal arrangement.

nervous system

The nervous system should also be examined using magnetic resonance imaging (MRI) or computed tomography (CT). A conspicuous brain structure, such as is present in a holoprosencephaly, can thus usually be recognized.

skeletal system

Malformations of the skeleton are often examined only recently because they represent in most cases no acute threat to life. Bones can be displayed well on x-rays.

Trisomy 13: treatment

There is no curative treatment for trisomy 13. The aim of all efforts is to provide the best possible quality of life for the affected baby. Any treatment for Trisomy-13 should be done by an experienced multidisciplinary team. This team includes gynecologists, paediatricians, surgeons and neurologists. In addition, palliative care physicians can make a very important contribution to the well-being and comfort of the child.

While malformations of the organs in the chest and abdomen are often treatable and operable, the malformations of the central nervous system (especially in the brain) represent a major challenge. They are usually not therapierar.

Generally, the therapeutic measures depend on the expression of the various malformations. The treatment should always be planned individually. In detailed discussions, the various problems are discussed and evaluated according to your urgency. In the literature, the type and intensity of therapy are controversial.

Since the mortality of the disease is very high, treatment limits are often matched with the parents. Ideally, however, this should be done gradually. It is discussed, for example, whether and what surgery (e.g., on the heart) is currently being performed for treatment or which should be waived in the child’s best interest.

Accompanying the parents

Very important is also an accompaniment of the parents. They should be offered help and support in a responsible and honest manner, for example by social workers or in the form of psychological support. If the parents initially feel overwhelmed and helpless, the crisis intervention service can give hope and orientation.

Trisomy 13: Disease course and prognosis

The Pätau syndrome is not curable. Many of the prenatal diagnosed trisomy 13 cases die before birth, many more in the first month of life. Only five percent of babies are older than 6 months. More than 90 percent of those affected die in the first year of life. However, it is hard to predict how long a trisomy 13 baby will survive.

On average, the trisomy 13 life expectancy of a baby born alive is 90 days after birth. This is mainly because of the fact that serious complications of the malformations usually occur directly after birth. The most common life-threatening complications of Trisomy 13 include difficulty breathing, heart failure, seizures, kidney failure, and feeding problems. Intensive care may prolong survival.

Longer survival is possible, especially if there is no major brain malformation. But even trisomy 13 children who survive the first year of life, often show a large intellectual deficit, so they usually can not lead an independent life.

Even if there is no cure, a variety of research into healing options are being conducted, which will one day be a therapy for the Trisomy 13 to find.