Trisomy 13: Description
Trisomy 13, also known as (Bartholin) Pätau syndrome, was first described by Erasmus Bartholin in 1657. In 1960, Klaus Pätau discovered the cause of trisomy 13 through the introduction of new technical methods: in trisomy 13, chromosome 13 occurs three times instead of the normal two. The extra 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 made up of DNA and proteins and are contained in the nuclei of almost all body cells. Chromosomes are the carriers of genes and thus determine the blueprint of a living organism.
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 referred to as either the X or Y chromosome.
In all trisomies, the number of chromosomes is 47 instead of 46.
What types of trisomy 13 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 13: In this form of trisomy 13, the additional chromosome is only present in a certain proportion of the cells. The other cells are equipped with a normal set of chromosomes. Depending on the type and number of cells affected, the symptoms of mosaic trisomy 13 can be significantly milder.
- Partial trisomy 13: In this form of trisomy 13, only one section of chromosome 13 is present in triplicate. Depending on the triple section, there are more or fewer symptoms.
- Translocation trisomy 13: Strictly speaking, this is not a true trisomy, but rather the rearrangement of a chromosome section. Only a 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 then referred to as a balanced translocation.
Occurrence
Trisomy 13: Symptoms
The list of possible trisomy 13 symptoms is long. The symptoms experienced by affected children depend on the individual case. The type and severity of the symptoms of trisomy 13 can vary depending on the form of the disease. The more cells are affected, the more severe the consequences. In the case of mosaic and translocation trisomies, the severity of symptoms may be so low that hardly any impairment is noticeable.
A free trisomy 13, on the other hand, is associated with severe malformations and disorders.
The classic symptom complex is the simultaneous occurrence of the following signs:
- Small head (microcephaly) and small eyes (micropthalmia)
- Cleft lip and palate
- Extra fingers or toes (polydactyly)
These malformations are typical for trisomy 13, but do not always have to be present. Numerous other organ systems can also be affected.
Face and head
In addition to microphthalmia, the eyes may be very close together (hypotelorism) and covered by folds of skin. The two eyes may be fused into one (cyclopia), which is often accompanied by malformations of the nose (possibly a missing nose). The nose can also appear very flat and wide with trisomy 13.
In addition, the ears are often conspicuously shaped due to their relatively low position, as is the chin.
Central nervous system
The small head and the lack of separation of the cerebral hemispheres can also lead to hydrocephalus. In addition, the neurological limitations often cause the affected children to have particularly flaccid muscles (hypotonia). All this makes it difficult to make contact with the child.
Internal organs
The internal organs in the chest and abdominal cavity are also affected by trisomy 13. A number of different malformations (e.g. rotated arrangement of the organs in the abdominal cavity) can lead to considerable restrictions in daily life.
Heart
80 percent of patients with trisomy 13 have heart defects. These are mainly defects in the walls separating the four chambers of the heart (septal defects). A so-called persistent ductus arteriosus is also common. This is a type of short circuit between the vessel (pulmonary artery) leading from the heart into the lungs and the main artery (aorta).
This short circuit makes sense in the fetus, as the unborn child does not breathe through the lungs, but receives oxygen-rich blood from the mother. After birth, however, the ductus arteriosus normally closes with the first few breaths. If this does not happen, it can dangerously disrupt the newborn’s blood circulation.
Kidney & urinary tract
Genital organs
In a male newborn, the testicles may fail to descend naturally from the abdomen into the scrotum. This normally occurs as part of natural development in the mother’s womb. If left untreated, this can result in sperm development disorders or even infertility. The scrotum can also be abnormally altered. Female newborns may have underdeveloped ovaries (ovaries) and a malformed uterus (bicornuate uterus).
Hernias
A hernia is the displacement of abdominal tissue through a natural or artificial gap in the abdominal wall. In the case of trisomy 13, hernias mainly occur around the navel, in the groin and at the base of the navel (omphalocele).
Skeleton
The skeleton is also not exempt from the consequences of trisomy 13. Numerous malformations of the bones are possible. In addition to an additional sixth finger (or toe), the hands and fingernails are often severely deformed. This sometimes leads to the outer fingers pointing towards the middle and lying on top of the inner fingers, so to speak. The foot can also be malformed in the form of a clubfoot.
Blood vessels
Trisomy 13: causes and risk factors
The majority of trisomy 13 cases are the result of an error in the formation of the gametes, i.e. the sperm and egg cells. These two cell types normally only have a single (half) set of chromosomes with 23 chromosomes. During fertilization, a sperm cell fuses with an egg cell so that the resulting cell contains a double set of 46 chromosomes.
To ensure that the gametes only have a single set of chromosomes before fertilization, their precursor cells must divide into two gametes, separating each pair of chromosomes. Errors can occur during this complicated process, for example, a pair of chromosomes may not separate (non-disjunction) or part of one chromosome may be transferred to another (translocation).
After a non-disjunction, one of the resulting gametes contains two chromosomes of a certain number, in this case number 13. In the other cell there is no chromosome 13 at all. Accordingly, one carries 24 chromosomes and the other only 22.
In the case of mosaic trisomy 13, the error does not occur during the division of the sex precursor cells, but at some point during the further development of the embryo. Many different cells already exist, one of which suddenly fails to divide correctly. Only this cell and its daughter cells have the wrong number of chromosomes, the other cells are healthy.
There is no clear answer as to why some cells do not divide properly. Risk factors include an older age of the mother during fertilization or pregnancy and certain substances that can disrupt cell division (aneugens).
Is trisomy 13 hereditary?
Although a free trisomy 13 is theoretically hereditary, those affected usually die before reaching sexual maturity. A translocation trisomy 13, on the other hand, can be asymptomatic. A carrier of such a balanced translocation is unaware of the genetic defect, but is likely to pass it on to their offspring. There is then an increased risk of a pronounced trisomy 13. A special genetic test can be carried out to determine whether a translocation trisomy 13 is present.
Trisomy 13: examinations and diagnosis
Specialists for trisomy 13 are specialized paediatricians, gynaecologists and human geneticists. Trisomy 13 is often diagnosed during pregnancy as part of preventive examinations. By the time of birth at the latest, external changes and malfunctions of the cardiovascular system are usually noticeable. However, mosaic trisomy 13 can also be relatively inconspicuous.
Prenatal examinations
In many cases, trisomy 13 is already suspected during prenatal examinations. The thickness of the fetal nuchal fold is routinely measured during ultrasound examinations of pregnant women. If this is thicker than usual, this already indicates a disease. Various blood values may provide further information and finally certain pathological organ changes confirm the suspicion of trisomy 13.
Genetic tests
If there are indications of trisomy 13, prenatal genetic counseling including prenatal testing is recommended. This involves using special techniques to take cells from the amniotic fluid (amniocentesis) or placenta (chorionic villus sampling) and subjecting them to DNA analysis. Such invasive prenatal examinations provide very reliable results, but can trigger a miscarriage.
Examples of such blood tests are the Harmony test, Praena test and Panorama test. If there is reasonable suspicion of trisomy 13 and after a medical consultation, the costs incurred for such a prenatal test can be covered by statutory health insurance.
Postnatal examinations
After birth, it is initially important to detect life-threatening malformations and developmental disorders that require immediate treatment. For this reason, a thorough examination of the newborn’s organ systems is carried out. The prenatal examinations also help to assess the severity of trisomy 13. After birth, the affected child usually requires intensive medical monitoring and treatment.
If trisomy 13 has not already been detected during the prenatal check-ups, the genetic test is carried out after birth. A blood sample from the newborn is sufficient for this, which can be taken from an umbilical vein, for example.
Heart
The heart must be examined in detail as soon as possible after birth. Cardiac ultrasound (echocardiography) can be used to assess the malformations of the heart. In particular, the partitions in the heart should be examined closely. Serious heart disease often manifests itself in dangerous circulatory disorders that require intensive medical treatment.
Gastrointestinal tract
Nervous system
The nervous system should also be examined using magnetic resonance imaging (MRI) or computer tomography (CT). An abnormal brain structure, such as is present in holoprosencephaly, can thus usually be detected.
Skeletal system
Malformations of the skeleton are often only examined in more detail at the last stage, as in most cases they do not pose an acute threat to life. Bones can be easily visualized on x-rays.
Trisomy 13: Treatment
There is currently no curative treatment for trisomy 13. The aim of all efforts is to achieve the best possible quality of life for the affected baby. Any treatment for trisomy 13 should be carried out by an experienced, multidisciplinary team. This team includes gynecologists, pediatricians, surgeons and neurologists. Palliative care physicians can also make a very important contribution to the child’s well-being and comfort.
While malformations of the organs in the chest and abdomen are often treatable and operable, malformations of the central nervous system (especially in the brain) pose a major challenge. They are usually not treatable.
As the mortality rate of the disease is very high, treatment limits are often agreed with the parents. Ideally, however, this should be done step by step. For example, it is discussed whether and which operation (e.g. on the heart) should currently be carried out for treatment or which should be avoided in the interests of the child.
Support for the parents
It is also very important to support 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 provide hope and guidance.
Trisomy 13: course of the disease and prognosis
Pätau syndrome cannot be cured. Many of the prenatally diagnosed cases of trisomy 13 die before birth, many more in the first month of life. Only five percent of babies live beyond the age of 6 months. More than 90 percent of those affected die in the first year of life. However, it is almost impossible to predict how long a trisomy 13 baby will survive.
Longer survival is possible, especially if there are no major brain malformations. However, even trisomy 13 children who survive the first year of life often show a major intellectual deficit, meaning that they are usually unable to lead an independent life.
Even though there is still no cure, a large number of studies are being carried out to research possible cures with the aim of one day finding a therapy for trisomy 13.
