What are chromosomes?
Chromosomes can be thought of as “packages” of genetic information stored in the nuclei of cells.
- A person usually has 46 chromosomes (23 pairs).
- One chromosome in each pair comes from the mother and the other from the father.
- Reproductive cells (egg cells and sperm cells) have 23 chromosomes — at conception, they combine to form pairs.
What is a karyotype?
A karyotype is the “arrangement of chromosomes” according to their size and characteristic banding patterns, which can be seen under a microscope.
- Female: 46,XX
- Male: 46,XY
What changes can a karyotype detect?
1) Changes in chromosome number — aneuploidy
Most cells in the human body usually contain 46 chromosomes, arranged in 23 pairs. Sometimes, however, a chromosome may be missing, or an extra chromosome may be present. This type of change is called aneuploidy.
Most commonly, this involves a trisomy — instead of the usual two copies, there is a third copy of a particular chromosome. The cell then has a total of 47 chromosomes.
These changes usually occur newly and at random, most often during the formation of an egg cell or sperm cell, or during the first divisions of the embryo. The risk of some trisomies increases with the woman’s age.
The best-known trisomies include:
- trisomy 21 — Down syndrome
- trisomy 18 — Edwards syndrome
- trisomy 13 — Patau syndrome
Many numerical chromosomal abnormalities, however, do not result in the birth of a baby, and the pregnancy may end in a very early or spontaneous miscarriage.
Karyotype testing can detect these larger changes in chromosome number.
2) Changes in chromosome structure
In addition to changes in chromosome number, changes can also occur in the structure of chromosomes. A chromosome can be thought of as a long segment of genetic information. If part of it is lost, duplicated, inverted, or moved elsewhere, this is called a structural chromosomal rearrangement.
Examples include:
- deletion — part of a chromosome is missing
- duplication — part of a chromosome is present in an extra copy
- inversion — part of a chromosome is turned in the opposite direction
- translocation — part of a chromosome moves to another chromosome, or two chromosomes exchange parts with each other
From a reproductive perspective, translocations are particularly important.
In some people, a translocation may be balanced. This means that the overall amount of genetic information is neither missing nor duplicated; it is simply arranged differently. A carrier of a balanced translocation may therefore be completely healthy and may not know about it at all.
The problem may become apparent during the formation of egg cells or sperm cells. Some reproductive cells may then have an unbalanced chromosomal complement, where a particular part of the genetic information is missing or present in an extra copy.
This can lead to:
- infertility
- recurrent miscarriages
- repeated unsuccessful IVF cycles
- recurrent chromosomal abnormalities in embryos
- an increased risk of a chromosomal abnormality in offspring
Therefore, when a structural chromosomal rearrangement is suspected, karyotype testing is often recommended for both partners. The result helps determine whether, for example, a balanced translocation is present and allows the doctor or geneticist to recommend the most appropriate next steps.
Inheritance
Chromosomal changes may be inherited from the mother or father, or they may arise newly, meaning de novo.
So-called balanced rearrangements are especially important: the carrier may be completely healthy because no genetic information is “missing or duplicated”; it is simply arranged differently. However, some egg cells or sperm cells may still be formed with unbalanced genetic information — which may result in:
- infertility
- recurrent miscarriages
- or a higher risk of a chromosomal abnormality in offspring
For this reason, karyotype testing is often recommended for both partners.
Who is karyotype testing suitable for?
Karyotype testing may be recommended especially in situations where it is necessary to assess the number or structure of chromosomes.
It is most commonly performed in:
- couples with infertility, especially if they have been trying to conceive for a long time or if treatment with assisted reproduction methods has been unsuccessful
- couples with recurrent pregnancy loss, meaning repeated miscarriages or missed miscarriages
- couples with a family history of a chromosomal rearrangement or chromosomal abnormality
- parents of a child with a chromosomal abnormality, or following a pregnancy in which a chromosomal abnormality of the fetus was detected
- individuals with a disorder of sex development, delayed or absent puberty, or suspected changes in the number of sex chromosomes
- women with premature ovarian insufficiency or markedly reduced ovarian reserve, if a chromosomal cause is suspected
- men with a significantly abnormal semen analysis, especially in cases of very low sperm count or absence of sperm in the ejaculate
Testing may also be appropriate when chromosomal abnormalities repeatedly occur in embryos during IVF.
The indication is always determined by a doctor or clinical geneticist based on the individual situation.
What happens next if a chromosomal abnormality is found?
Finding a chromosomal abnormality does not always automatically mean a serious health problem. It depends on the type of change, whether it arose newly or was inherited, and whether the change is balanced or unbalanced.
Genetic counselling is therefore an important part of the next steps. During the consultation, the clinical geneticist will explain:
- what the specific finding means
- whether it may be relevant to your health
- what the risk may be for a pregnancy or child
- whether it is appropriate to test your partner or other family members
- and what further options are available
If the reproductive risk is significantly increased, treatment with assisted reproductive technologies (IVF) may be recommended, with the option of preimplantation genetic testing of embryos. For structural chromosomal rearrangements, such as translocations, PGT-SR is used in particular. The aim is to select an embryo with a balanced chromosomal complement for transfer.
What a karyotype typically does not address
A karyotype assesses large-scale changes in chromosome number and structure. It does not detect all small genetic changes, such as small changes in individual genes. These require other types of testing, which your clinical geneticist will recommend based on the indication.
