Introduction
Mosaicism occurs when an individual's cells exhibit diverse genetic compositions. In this scenario, some cells may possess 46 chromosomes, while others carry 47. This disparity in chromosomal makeup can give rise to health complications during birth, such as Mosaic Down syndrome, and may also lead to issues later in life.
Which Disorders Are Associated With Mosaicism?
Mosaicism can lead to various disorders, each with its own set of symptoms. Some examples include:
Ichthyosis With Confetti: This disorder results in red, scaly skin covering the entire body.
Mosaic Klinefelter Syndrome: This syndrome may lead to lower testosterone levels, causing issues with sexual development and other complications.
Klippel-Trenaunay Syndrome: This disorder is characterized by a red birthmark (port-wine stain), excessive growth of soft tissues and bones, and abnormal veins.
Mosaic Down Syndrome: Known for intellectual disabilities, delayed development, weak muscles, and distinctive facial features. It can also involve heart defects, digestive issues, and thyroid problems.
Pallister-Killian Syndrome: A developmental disorder causing weak muscles, intellectual disability, thin hair, patches of abnormal skin color, and other birth defects.
Mosaic Ring Chromosome 14 Syndrome: This condition manifests as seizures, intellectual disability, and delayed speech and motor development.
SOX2 Anophthalmia Syndrome: A rare disorder resulting in the absence of eyeballs at birth, along with seizures, brain issues, and delayed growth.
Mosaic Triple X Syndrome: Caused by an extra X chromosome in each cell of females, leading to learning disabilities, delayed language skills, and problems with motor skills and muscles.
Mosaic Trisomy 18: This condition can cause slow growth in the womb, heart defects, a small head, and other defects. Sadly, only a small number of children with this condition live past their first year.
Mosaic Turner Syndrome: A condition in females characterized by short height, ovarian problems, infertility, and heart defects.
The impact of mosaicism on a person's health depends on the level of mosaicism present at birth. It has been associated with various conditions like Turner syndrome (a chromosomal abnormality) and different forms of cancer. Potential symptoms may also include blood cancers, birth defects, developmental delays, and possible miscarriages.
What Causes Mosaicism in Humans?
Mosaicism in humans arises during pregnancy, specifically after the egg's fertilization and the zygote's initial division. This process involves forming new cells and replicating chromosomes to ensure the new cells have the same chromosome count as the original cell. However, variations can occur during this stage, leading to mosaicism, where cells have different chromosome numbers. In some cases, abnormal cells may die without causing issues, but when they persist, mosaicism develops.
There are two levels of mosaicism: high-level and low-level. High-level mosaicism results from abnormal cells in early development, affecting 50 percent or more cells. On the other hand, low-level mosaicism occurs later, impacting a smaller number of cells.
What Are the Types of Mosaicism?
There are different types of mosaicism, each with its own characteristics; in the developmental stage, there are two types of mosaicism:
1. Somatic Mosaicism: This occurs when multiple somatic cell lineages are involved, but it does not affect the sperm and eggs. Importantly, it does not impact the offspring. However, if somatic mosaicism happens during preimplantation, the embryo's somatic (body) and germline (reproductive) cells may be affected.
2. Germline Mosaicism: In this type, more than one cell lineage of the germline cells is affected, potentially influencing the offspring.
3. Cellular Stage Mosaicism: Mosaicism at the cellular stage is categorized into two types:
General Mosaicism: This occurs when a baby has two or more different cell lines.
Confined Mosaicism: Unlike general mosaicism, this type affects specific body parts or organs, such as the brain, heart, or liver, while leaving other organs unaffected.
Predicting who will develop mosaicism is currently not possible. However, in the context of in-vitro fertilization (IVF), doctors can perform a preimplantation genetic screening (PGS) before placing the fertilized egg into the woman's uterus. This screening helps assess the risk of mosaicism, providing valuable information during the IVF process.
How to Diagnose Mosaicism?
Mosaicism is diagnosed through genetic testing involving blood and skin tests. Sometimes, two different tissues may need testing. Tests may need to be repeated to confirm mosaicism's presence, type, and severity. In pregnant women, prenatal diagnosis can be conducted on embryos up to eight to ten weeks old. Tests like amniocentesis and chorionic villus sampling determine if an embryo is a mosaic without removing any embryo tissue. Given the increased risk of mutation and mosaicism with in-vitro fertilization, preimplantation screening is crucial to prevent genetic disorders.
What Is the Treatment for Mosaicism?
At present, there is no cure or guaranteed prevention for mosaicism. Treatment approaches depend on the type and severity of mosaicism. Less aggressive treatments are suggested for instances where less than half of the cells are affected. Conversely, more intense treatment methods are considered for severe cases.
What Is the Prognosis of Mosaicism?
The outlook for individuals with mosaicism varies based on the severity of the disorder, the specific type, and the organs or tissues involved. Those with a lower count of irregular cells may experience milder effects than those with a higher count. It is important to highlight that mosaicism can impact the survival rate for monosomies. While monosomies are typically fatal, mosaic monosomies can survive after birth. Additionally, mosaicism has the potential to contribute to the development of malignancies.
Conclusion
Mosaicism is a complex genetic phenomenon with profound implications for human health. The diverse range of associated disorders, from Ichthyosis with Confetti to Mosaic Turner syndrome, underscores the intricate nature of genetic variations. Understanding the causes and types of mosaicism, whether somatic or germline, provides essential insights into its developmental stages and potential impacts on offspring. While predicting mosaicism remains challenging, advancements in genetic testing, particularly in the context of in-vitro fertilization, offer valuable tools for assessing and managing associated risks. Despite the absence of a cure, tailored treatment approaches and the variable prognosis highlight the need for personalized care based on the severity and type of mosaicism.
