Genetic Basis

Chromosome 18 conditions are caused by a change in a person’s genetic makeup. On this page, you will learn more about the genetic basis of chromosome 18 conditions.


Chromosomes are the structures that hold all of our genes. Genes are simply the instructions that tell the body how to grow and develop. They do this by telling the body how to make a protein. For example, genes are the instructions for visible things, like hair and eye color. They are also the instructions for things that we can’t see, such as proteins for digesting food. Chromosomes are located in the cells of the body. Chromosomes, and the genes that are located on them, are passed from parent to child through the egg and the sperm.
We have 46 chromosomes. These 46 chromosomes are arranged in pairs. We have 23 pairs of chromosomes. We inherit one copy of each pair from our mother and the other copy from our father. Each chromosome is different from other chromosomes. They each carry a different set of genes.

In addition, chromosomes look different from each other under the microscope. Some chromosomes are larger than other chromosomes. In addition, each of the chromosomes has a unique banding pattern. These bands are used to identify the different sections of each chromosome. Near the center of each chromosome is a constricted region that divides the chromosome into two arms. The constricted region is called the centromere. The shorter arm of each chromosome is called the “p” arm, and the longer arm of the chromosome is called the “q” arm.

A chromosome abnormality is a change in the number or the arrangement of the chromosomes. There are many different types of possible changes. In some individuals, a piece of a chromosome is missing. This is called a deletion. In other individuals, a piece of a chromosome is duplicated. This is called a duplication. Sometimes, there are more complicated rearrangements of the chromosomes. Some examples of other chromosome rearrangements are translocations, inversions, and insertions.


Chromosome abnormalities are actually quite common. The majority of chromosome changes happen either in the egg or sperm before conception or shortly after fertilization. In fact, up to 50% of all conceptions carry some kind of a chromosome change. However, the grand majority of those conceptions do not result in a pregnancy. The embryos either do not implant, or they are miscarried, usually early in a pregnancy. We estimate that chromosome changes happen in one in 180 liveborn babies.

Some parents are concerned that they did something to cause the chromosome change. There are no data to suggest that a parent’s choices before or during a pregnancy can cause a chromosome

The only risk factor for chromosome changes is a mother’s age. As a woman gets older, the risk for a specific type of chromosome change increases. Older mothers have a higher likelihood of having a child with a trisomy. A trisomy occurs when an entire extra copy of a chromosome is present. For example, in trisomy 18, there are three copies of chromosome 18 instead of two.


In the past, the majority of chromosome abnormalities were diagnosed by a karyotype. A karyotype is simply a picture of a person’s chromosomes. In order to get this picture, the chromosomes are isolated, stained, and examined under the microscope. Most often, this is done using the chromosomes in the white blood cells.

Karyotypes are still used in the diagnosis of chromosome abnormalities. However, a newer technology has been developed that is also frequently used in the identification of chromosome abnormalities. This technology is called a microarray.

A microarray analysis compares a person’s DNA to “control DNA”. The control DNA comes from a person that doesn’t have a chromosome abnormality. A chromosome change is identified when there are differences between a person’s DNA and the control DNA.

FISH analysis is another tool that can be used to characterize chromosome changes. This technology uses a probe to determine whether a certain part of the chromosome is present or absent. As other technologies, such as microarray, have been developed, FISH analysis is used less frequently. However, it may still be used to examine balanced rearrangements, such as translocations or inversions.






Microarrays are useful in that they are able to detect much smaller changes than routine karyotypes or FISH analysis. They tell us if there are changes in the amount of DNA present. They can identify deletions or duplications as well as unbalanced translocations. Microarray technology can also be used to learn more precise information about abnormalities that have already been diagnosed by karyotype. However, microarrays cannot diagnose balanced translocations or rearrangements. This is because there is no change in the amount of DNA present, only a change in location and arrangement.





At this point, we know that a chromosome abnormality may be suspected when a child has developmental delays or unexplained medical problems. But how exactly does a chromosome change lead to these issues?

As discussed above, genes are responsible for telling the body how to make proteins that play a role in various parts of the body. When a piece of a chromosome is missing or duplicated, the genes that are located in that region are also missing or duplicated. This means that there will be too little or too much of the proteins that are coded by those genes.

As it turns out, a missing or extra copy of a gene does not necessarily cause problems. In fact, we believe that only about 10% of genes, when deleted or duplicated, cause issues. Chromosome 18 has about 300 genes, so we estimate that along the entire chromosome, there are only about 20-30 genes that actually have an effect when they are duplicated or deleted. The key is to identify which genes they are and how they lead to medical and developmental problems.


For a long time, people thought that chromosome conditions were untreatable. It is true that we are unable to replace missing pieces of a chromosome or remove extra pieces of chromosome.
However, we may be able to modify their expression, i.e. the amount of protein made from the gene(s). For example, when one of the two copies of a gene is deleted, the result is usually less protein expression. If we can somehow find a way to “up-regulate” the remaining gene, the protein expression can return to normal, and some of the effects of that deletion will be reversed. Conversely, if there is a gene duplication, we may find a way to “down-regulate” the extra copies of the gene, that is, keep them from overexpressing its protein.





The Chromosome 18 Clinical Research Center is dedicated to understanding chromosome 18 conditions and to developing treatments. This is a long process. We must collect data on the natural history of the chromosome 18 conditions; identify the key genes responsible for those features; and identify drugs that can regulate those genes. With the help of families with chromosome 18 conditions, The Research Center has already made great progress towards our goals.