Mosaic RASopathies

What Are RASopathies?

RASopathies are a group of genetic conditions so named because they are caused by problems in the RAS pathway. In living things, a pathway is a series of actions between chemical messengers that can lead to a specific change or response in that cell. The RAS pathway provides a way for the cells of our body to communicate that is essential to their function. This means it is important for proper growth, development and good health.

RASopathies impact numerous body systems, including the heart and blood vessels (cardiovascular), glands and hormones (endocrine) and nervous systems. They vary widely in their signs and symptoms and the way they appear across people who have one of the RASopathies. Mosaic RASopathies may be less apparent than the classic or typical syndromes, such as Costello and Noonan syndromes.

What Is Mosaicism?

Genes are made of DNA sequences that carry the instructions for the cells of our bodies to make protein products we need to grow and function properly. Genes come in pairs, and we inherit one copy from our mother and another from our father. After an egg cell from our mother is fertilized by a sperm cell from our father, it begins to divide and replicate, making multiple exact copies of the cell’s DNA. In time, many cells form the tissues and organs of the fetus. It is at this stage that mosaicism can occur. It happens by chance and is not caused by anything done by either parent.

In most cases, our bodies have a full set of identical genetic material that is present in every cell. However, mistakes happen sometimes when cells divide and replicate, which lead to genetic differences in those cells. When this type of error happens, a cell may have extra or less genetic material than the others. As that cell continues divide and replicate, it will create more and more copies of itself that have the altered genetic material. The result is mosaicism, meaning the body has two or more sets of cells that are genetically different from one another.

For example, a person could have 70% typical cells and 30% mosaic cells. The fraction of mosaic cells to typical cells is called the level of mosaicism. When the error in cell division happens earlier in fetal development, there are higher levels of mosaicism. When it happens later in fetal development, there are lower levels.

What Are the Signs & Symptoms of a Mosaic RASopathy?

The signs and severity of symptoms for a mosaic RASopathy depend largely on:

When the error in cell division occurred in development
The cell types affected (such as skin, brain or heart cells)
Where the mosaic cells are in the body

If the genetic change present in the mosaicism is in a part of the RAS pathway that is more vital to the body’s normal function, then the mosaic RASopathies may be more severe. Severe cases may also carry an increased life-time risk for some cancers. For example, someone who has mosaic segmental NF1 may have a higher risk for a certain types of cancer, including brain, breast and a sarcoma called malignant peripheral nerve sheath tumors (MPNST).

For some of the mosaic RASopathy conditions, such as mosaic or segmental NF1 and mosaic Costello syndrome, the signs and symptoms are nearly identical to their classic counterparts without mosaicism. Yet, this also varies from person to person.

How Is Mosaicism Diagnosed?

A doctor who specializes in genetic disorders or a genetic counselor may suspect that a RASopathy is mosaic, but this can only be confirmed through genetic testing. Genetic testing is done on a blood sample and may also include testing of a sample of the affected tissue, depending on the location of the tissue. The results of genetic testing can provide an estimate of the level of mosaicism.

Treatments and Long-Term Effects of Mosaic RASopathies

As with the other RASopathy conditions, there is no single treatment for any of the mosaic RASopathies. Treatment is based on the symptoms and the concerns of the medical provider, patient and family. The long-term effects of each mosaic RASopathy also vary case by case. Factors include the severity of the signs and symptoms, and the level of mosaicism.

Research

Our team works closely with researchers who study RASopathies, including mosaic RASopathies. Thus, we are informed of cutting-edge technology and treatments that may benefit the children in our care. We can connect interested children and families with opportunities to participate in research studies that can help us better understand the RASopathies and possibly contribute to the discovery of future treatments.