Chromosome microarray testing is ordered when someone – usually an infant – is found to have a developmental delay, intellectual disability, autism or at least two congenital anomalies (physical issues which the child was born with), and a diagnosis cannot be made by information from clinical examination or other tests.
A quick look at genes and chromosomes
Our bodies are made up of trillions of cells. Almost every cell has a nucleus (a sac in the middle of the cell) containing a complete set of genetic material in genes. Genes are the chemical instructions that tell your body how to make all the different parts it needs to function. Genes are short sections of DNA and our DNA is packaged into structures called chromosomes
Usually, our cells have a set of 23 pairs of chromosomes or 46 chromosomes. There are 22 pairs of chromosomes which are the same in both males and females, these are called autosomes and one pair of sex chromosomes - a pair of X chromosomes in females (XX) and one X and one Y in males (XY).
How genes and chromosomes are passed from parents to children
Chromosomes are inherited from our parents. We get one copy of each chromosome from our mother (22 autosomal chromosomes and an X chromosome, via the egg), and another copy of each chromosome from our father (22 autosomal chromosomes and either an X or a Y chromosome, via the sperm).
While typically cells have 46 chromosomes, sperm and egg cells are different. They have only 23 chromosomes. When a sperm cell and an egg cell fuse in conception, they each bring 23 chromosomes to form a fertilised egg that has a full set of 46 chromosomes. Combining genetic information from both parents in this way ensures genetic diversity.
Chromosomal changes
Chromosomal changes can occur when the egg or sperm cells are made inside a person’s body, or in the early stages of conception after an egg has been fertilised. When this happens, these changes (called genetic variants or mutations) are present in every or nearly every cell in a person’s body. These are called germline genetic variants.
Chromosomal changes can also occur during the normal course of life. These are called acquired or somatic genetic changes.
Our cells have a lifespan – they get old and die off. Some cells last only a few hours or days, while others last for months or years or even a lifetime. The cells in our bodies are constantly dividing to make new cells. Each time a cell divides, it copies its DNA and sometimes small copying mistakes can occur, called variants. Some cells may have unstable chromosomes that can lead to alterations taking place when the cell is copying itself - this is often seen in cancer. These genetic changes that happen during a person’s life are called somatic variants.
When changes happen, whole chromosomes may be lost or added, meaning a person is born with one more or one less chromosome than the usually 46 chromosomes. Other changes can happen when pieces of a chromosome are rearranged within one chromosome or transferred between two or more chromosomes. Small pieces of a chromosome may be lost, or an extra piece added, resulting in too little or too much genetic information. Some of these changes can cause health and developmental problems, while others may have no effect on a person's health.
The way these chromosomal changes impact on our health is very varied and depends on which chromosome has been changed and in what way.
Different types of chromosome testing
There are three main types of tests used to assess chromosomal changes:
Karyotyping (chromosome studies)
Karyotyping visually examines the number and structure of chromosomes under a microscope. It uses staining techniques to produce a picture of all 46 chromosomes arranged in pairs, called a karyotype.
Karyotyping was developed many years ago and the resolution is relatively low compared to more modern techniques. This means it cannot detect small deletions or duplications. It has largely been replaced by tests like CMA and in some cases whole genome or exome sequencing, but it is still used for certain chromosomal changes that cannot be picked up by CMA.
Karyotyping is better than CMA when you need to see balanced structural changes.
What it detects:
Large chromosomal changes, such as:
When it is used:
For more see Karyotyping (Chromosome studies)
Chromosome microarray testing (CMA)
This uses DNA probes on a chip to detect small gains or losses of chromosome segments. CMA is more sensitive than karyotyping. Although both techniques are able to examine all chromosomes, CMA can detect very small changes that cannot be seen through a microscope. These small changes are called copy number variations or CNVs. They can range in size from very small pieces of DNA to large parts of a chromosome or even the loss or gain of an entire chromosome.
If the detected CNV has previously been reported and classified, it may be described as:
The genetics specialists interpreting the test will look at the laboratory report to see if the changes found are known to be associated with the problems the patient is having. These CNV changes will be reported as either pathogenic or likely pathogenic, depending on how much evidence there is to link the CNV to the condition.
CMA cannot detect balanced rearrangements like translocations or inversions where chromosome pieces are swapped evenly (not parts of the chromosome are gained or lost). Karyotyping is needed for this.
Neither can it detect single-nucleotide mutations (point mutations) or very small sequence changes.
When is CMA testing used?
CMA is also used in prenatal testing when ultrasound shows structural changes or to investigate an increased-probability non-invasive prenatal screening (NIPS) result.
Whole genome or exome sequencing
WGS and WES read almost every gene in the entire genome. Based on technology that allows the rapid sequencing of large amounts of DNA, they offer the highest resolution of all genetic tests and can be used to identify very small sequence changes.
WGS/WES is often used as a second-line test when other tests have failed to identify the genetic cause of global developmental delay, intellectual disability or congenital conditions. For more see Whole Genome and Exome Sequencing.
Sample
A blood sample. Sometimes cells are obtained through amniocentesis or chorionic villus sampling from a pregnant woman. Where it is technically difficult to obtain a blood sample (e.g. children with severe autism, young babies) a saliva sample or cheek swab can be used, but this is dependent on the laboratory.
Any preparation?
None.
For most people, the results from a microarray test give a negative result which means that no clinically significant CNVs – missing pieces or additional pieces of DNA - have been detected. (Most people will have one or two benign CNVs present. Benign or likely benign changes will not be reported but are commonly detected.)
If the microarray test does find that there is possibly missing or additional DNA, the next step is to further assess them.
Not all missing or additional pieces of DNA cause problems. Some can be present in a person or multiple members of a family without causing any problems at all.
The genetics specialists interpreting the test will look to see if the changes found are known to be associated with the problems the patient is having. They will also take into consideration the genes known to be located within the CNV segment that has been found. In many cases, the same results will have been seen in other people, and the test result will allow a diagnosis to be made.
However, sometimes the significance of the changes found is unknown. This happens quite often because the human genome is enormous – it contains three billion base pairs– so there are many places for variations to occur.
If a copy number variant of unknown significance is found, the parents of the child can be tested. If one of them has an identical variant in their DNA but does not have the medical problems found in the child, the variant is less likely to be the cause of the child’s problems.
Terms you may see on your report
| Term | Meaning |
| Trisomy | There is a whole extra chromosome, so there are three copies instead of two. Conditions associated with trisomies include Down syndrome (trisomy 21), Patau syndrome (trisomy 13) and Edward syndrome (trisomy 18). |
| Monosomy | A chromosome is missing. An example of monosomy is Turner syndrome (a female with a single X chromosome – X instead of XX). Most other monosomies are not compatible with life. |
| Deletions | There are missing pieces of chromosomes and/or genetic material. Some may be small and can be difficult to be detected. |
| Duplications | There is extra genetic material, and this may be on any chromosome, for example, two horizontal bands at a specific location instead of one. |
| Translocations | Pieces of a chromosome break off and reattach to another chromosome (called a rearrangement). Translocations can be balanced or unbalanced. A balanced translocation is a rearrangement where segments from two different chromosomes swap places without any gain or loss of genetic material. This means the person will not have an extra or any missing genetic material, but the genetic material is in a different place to where it is usually. People with balanced translocations are not usually affected, but it may lead to issues with fertility, recurrent miscarriage or health issues in their children as their children may inherit an unbalanced form of their translocation. An unbalanced translocation is where genetic material is gained or lost between chromosomes. This results in the person having too much or too little genetic material, which can affect development and health. |
| Inversions | A segment of a chromosome breaks in two places, flips around and reattaches to the same chromosome in the opposite direction. DNA may or may not be lost in the process. |
| Mosaicism | It is possible for people to have cells in their body with differing genetic material. This happens when genetic variations happen early in the development of a fetus, leading to that person having some cells with one type of genetic makeup and some cells with another type of genetic makeup. This is called mosaicism or mosaic genetic variation. For example, in some cases of Down syndrome a person can have some cells with an extra third copy of chromosome 21, and some cells with two copies of chromosome 21. Generally speaking, a person with mosaic genetic changes will not necessarily have less severe issues or symptoms than a person who has the genetic change in every cell in their body. However, in some disorders, mosaicism may mean symptoms are milder. |
Duplications, deletions, translocations and genetic rearrangements can cause health and development issues, depending on the genes that are missing or are present in too many copies.
Some genetic rearrangements will be variations that do not cause symptoms. Balanced translocations (where segments of two chromosomes have swapped positions, but all of the genetic material is present) may cause no problems for the person who has them but may cause problems in their children.
Although certain chromosome changes will cause typical issues or symptoms, the effects and the severity may vary and often cannot be known before a baby is born.
In Australia, the Medicare schedule will rebate microarray testing in a person, usually a child, with developmental delay, intellectual disability, autism, or at least two congenital anomalies.
Some laboratories may charge more than the Medicare rebate, so there may be an associated out of pocket expense. If the clinical information does not meet these guidelines, a fee will be changed. Test results can take some time to be delivered, and this can be up to two months.
The choice of tests your doctor makes will be based on your medical history and symptoms. It is important that you tell them everything you think might help.
You play a central role in making sure your test results are accurate. Do everything you can to make sure the information you provide is correct and follow instructions closely.
Talk to your doctor about any medications you are taking. Find out if you need to fast or stop any particular foods or supplements. These may affect your results. Ask:
Pathology and diagnostic imaging reports can be added to your My Health Record. You and your healthcare provider can now access your results whenever and wherever needed.
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