Mosaicism is a condition where a person has two or more genetically distinct cell populations originating from a single fertilized egg. Much like a mosaic artwork is composed of many different colored tiles to create a single image, the human body can be composed of genetically different cells. For instance, some cells in the body might have the standard 46 chromosomes, while others could have 47.
The Cellular Origins of Mosaicism
The development of mosaicism is not an inherited trait but the result of a random error during cell division very early in an embryo’s growth. This event happens during mitosis, as the initial fertilized egg, or zygote, begins to divide and a mistake causes chromosomes to distribute unevenly into the new cells. The genetic mutation arises spontaneously in one of the dividing cells as the embryo develops. This single altered cell then continues to divide, creating a lineage of cells that carry the mutation, while other cells in the body remain genetically typical.
Somatic and Germline Mosaicism
Mosaicism is broadly categorized into two main types based on which cells in the body are affected: somatic and germline. This distinction determines whether the genetic variation can be passed on to the next generation. It also influences how the condition might affect an individual’s own health.
Somatic mosaicism involves genetic changes present in the body’s cells (the soma) but absent from the reproductive cells (egg or sperm). These mutations can affect any tissue, such as the skin, brain, or blood. Because the genetic alteration is not in the germ cells, a person with somatic mosaicism will not pass the trait to their children. The effects of somatic mosaicism depend on which organ or tissue systems contain the altered cells.
In contrast, germline mosaicism, sometimes called gonadal mosaicism, is confined to the genetic material of the reproductive cells. The parent who carries the germline mutation is often unaffected and may be unaware of it, as the mutation is not in their other body cells. However, they can pass the genetic variant to their offspring, who may then have the condition in all of their cells (a constitutional mutation) and could be significantly affected.
Health and Developmental Implications
The impact of mosaicism on a person’s health and development exists on a wide spectrum, ranging from no noticeable effects to significant medical conditions. The severity and nature of these effects are determined by a combination of three factors: the specific gene or chromosome that is altered, the percentage of cells that carry the mutation, and which specific tissues or organs are affected.
For example, mosaic Down syndrome is a form of mosaicism where an individual has some cells with an extra copy of chromosome 21 and others with the usual two copies. People with this condition often experience milder features of Down syndrome compared to those who have the extra chromosome in all their cells. Their developmental delays and physical characteristics can be less pronounced.
At the other end of the spectrum are conditions like Proteus syndrome, a rare disorder associated with mosaicism in the AKT1 gene, which leads to overgrowth of various tissues, including bones, skin, and organs. Another example is Pallister-Killian syndrome, a developmental disorder that causes weak muscles, intellectual disability, and changes in skin pigmentation. The wide variability in outcomes underscores how the location and proportion of affected cells shape the clinical picture for individuals with mosaicism.
Detection and Diagnostic Challenges
Identifying mosaicism requires genetic testing, but the process can be complex. Because the genetic alteration may only be present in certain parts of the body, a test performed on a single tissue sample might not detect the condition. For instance, a standard blood test could miss mosaicism that is confined to the skin or brain cells.
To obtain an accurate diagnosis, clinicians may need to test samples from different tissues, such as a skin biopsy in addition to a blood sample. Prenatal testing, such as amniocentesis or chorionic villus sampling (CVS), can also identify mosaicism in a developing fetus, but these tests may also present challenges in interpretation. A finding of mosaicism in the placenta, for example, may not always reflect the genetic makeup of the fetus itself.
This diagnostic uncertainty is a challenge in managing mosaicism. Confirming a diagnosis often requires repeated tests on different cell types to determine the extent and distribution of the altered cells throughout the body. The difficulty in pinpointing the affected cells can make it hard to predict potential health outcomes.