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Chromosome Mosaicism


Inside every cell in the human body is a nucleus that contains a person’s genetic information—his or her DNA—inherited from an egg cell and a sperm cell. When the fertilized egg begins to divide, it replicates its genetic material in cellular offspring. This cell replication builds and builds, creating tissues and organs in the body. In theory, each replicated cell should contain the exact same genetic information as the fertilized egg. However, this is not always the case. In rare instances, new genetic changes can occur in these replicated cells. These changes occur on the chromosomes, which are structures that look like sticks and carry all of a person’s genetic information, located in each cell’s nucleus. 

Until recently, scientists thought the condition was straightforward—either a person had mosaicism or not. As genetic sequencing technology becomes more sophisticated, a picture is emerging in the field of genetics showing that we all have some amount of mosaicism. The more frequently mosaicism is found in the body, the greater likelihood a person can develop a health condition because of it. 

“Every mosaic situation has to be treated individually,” says Saquib Lakhani, MD, clinical director of the Yale Medicine Pediatric Genomics Discovery Program (PGDP). “If a patient has a disease related to the mosaicism, it has to be managed and understood in the context of that particular disease.”

At Yale Medicine, our physicians work with the Yale Center for Genome Analysis and researchers to provide the best possible care for genetic-related diseases. 

What is mosaicism?

Mosaicism occurs when a person has two or more genetically different sets of cells in his or her body. If those abnormal cells begin to outnumber the normal cells, it can lead to disease that can be traced from the cellular level to affected tissue, like skin, the brain, or other organs.

How does mosaicism occur?

Mosaicism likely occurs on some small, unnoticeable level in most humans. It happens after the sperm fertilizes an egg, forming a zygote, which grows through a process of cells dividing over and over and over. When cells divide and multiply, they make an exact copy of their DNA, and then split the copies between each of the resulting two cells. If there is a mistake anywhere in this process—for example, a DNA copy that contains a mistake or DNA that is split unevenly, the resulting cells would be different. In some cases, the abnormal cell may simply die; but, if it survives, the result is mosaicism. If this occurs early in development, as many as 50% of a person’s cells could be abnormal, which would be a high level of mosaicism. If the mistake happens later, however, a smaller percentage of cells would be abnormal, resulting in a lower level of mosaicism. The impact of mosaicism is typically determined by the severity of the mistake in the DNA, as well as the degree of mosaicism.

Who is at risk of mosaicism?

There is currently no way to predict mosaicism. Mosaicism is a topic that is often discussed during in-vitro fertilization (IVF) because physicians will usually perform a preimplantation genetic screening (PGS) before inserting the fertilized egg into the woman’s uterus. The woman will want to talk to specialists to understand the risks of mosaicism in embryos before implantation.  

What types of disorders are caused by mosaicism?

Mosaicism can cause many different kinds of disorders, including the following:

  • Ichthyosis with confetti. This is a disorder that causes red, scaly skin all over the body.
  • Klinefelter syndrome. This syndrome can cause low amounts of testosterone. This can lead to problems with sexual development and other issues.
  • Klippel-Trenaunay syndrome. This disorder causes a red birthmark called a port-wine stain. It also causes excess growth of soft tissues and bones, as well as abnormal veins.
  • Mosaic Down syndrome. Down syndrome is a condition that causes intellectual disabilities and delays, weak muscles, and flat facial features. It can also cause a heart defect, digestive problems, thyroid problems, and other health issues.
  • Pallister-Killian mosaic syndrome. This is a developmental disorder that causes weak muscles, intellectual disability, thin hair, patches of abnormal skin color, and other birth defects.
  • Ring chromosome 14 syndrome. This condition causes seizures, intellectual disability, and delayed speech and motor development.
  • SOX2 anophthalmia syndrome. This is a rare disorder that can cause a child to be born without eyes. It can also cause seizures, brain problems, and delayed growth.
  • Triple X syndrome. This condition is caused by an extra X chromosome in each of a woman’s cells. It can cause learning disabilities, delayed language skills, and problems with motor skills and muscles.
  • Trisomy 18. This condition can cause slow growth in the womb, heart defects, a small head, and other defects. Only a small number of children with this condition live past their first year.
  • Turner syndrome. This is a condition in women that causes short height, ovarian problems, lack of fertility, and heart defects.

How is mosaicism diagnosed?

Different methods can be used for diagnosing mosaicism. A blood test can be used to detect some kinds of mosaicism. In other cases, a sample of the affected tissue may need to be sent for genetic testing and examination. This would be necessary in a condition that affects the skin, such as ichthyosis with confetti. 

Which care options are available for mosaicism?

The care a patient receives for disorders caused by mosaicism will be specific to that particular condition. “If they are at risk for transmitting mosaic disease, that has to be understood in their context, with the help of a genetic counselor,” Dr. Lakhani says. 

What makes Yale Medicine unique in diagnosing this condition?

Yale Medicine offers patients the latest genetic sequencing technologies to help detect mosaicism and has medical geneticists and genetic counselors who can discuss possible care options with patients.