You might have heard of the TSC1 and TSC2 genes, which are linked to TSC. But the way TSC affects someone is more complicated than just these genes
Genes are like tiny instruction books inside our cells that tell the body how to work. TSC1 and TSC2 genes help control how cells grow, using a pathway in the body called mTOR, which that acts like a growth switch. Changes in these genes cause the tumours in TSC. But, TSC doesn’t affect everyone in the same way. In fact, even people with the same gene change can have very different experiences of the condition. In this article, we look at how TSC genetics shape people’s lives and why research to understand them is so important.
In people with TSC, the gene that acts as a brake on the mTOR pathway doesn’t work as it should, meaning cells tend to be larger and grow uncontrollably. This is what leads to TSC growths and tumours. There are more than 1,500 known changes in the TSC1 and TSC2 genes that can lead to a person having TSC. Therefore, even when two people have a change in the same gene, their experiences with TSC can be very different. One person might have seizures or developmental differences early in life, while another may not be diagnosed until adulthood. This wide variation, known as ‘variable expression’, is a normal part of TSC and helps explain why no two experiences are exactly alike.
How someone has TSC can also vary by large amounts. TSC can be inherited from a parent, but about two-thirds of cases happen due to a new genetic change that occurs for the first time in the affected person. Some individuals have mosaicism, meaning the gene change is present in only some of their cells. Mosaicism can result in milder symptoms, and in some cases, it can make diagnosis more challenging, as standard genetic tests may not detect the change in blood samples alone.
Knowing which gene is affected, TSC1 or TSC2, can sometimes help families understand the types of symptoms to monitor for and what will inform healthcare decisions. While TSC2 mutations are often associated with more noticeable symptoms, this is not always the case, and each person’s experience is unique.
Current research is exploring these interactions in more detail. Researchers are examining how different changes in TSC1 and TSC2 affect the mTOR pathway and organ development, as well as the role of mosaicism in causing milder or variable symptoms. Scientists are also investigating additional genetic and biological factors that may influence how the condition presents, using cell models, organoids (mini versions of organs grown in labs), and animal studies to test potential therapies before clinical trials. By combining genetic data with patient registries, researchers hope to better predict symptom patterns, personalise care, and ultimately improve monitoring, treatment, and quality of life for people living with TSC.
More broadly, genetic testing can also connect families with clinical trials, research opportunities, and new therapies as they become available. It helps doctors personalise care and monitoring, ensuring that individuals receive the right support for their specific needs.
While the genetics of TSC can be complex, every discovery brings us closer to improved care and treatment options. Understanding the role of TSC1 and TSC2 — along with the broader factors that influence the condition — empowers families to make informed decisions, connect with support networks, and participate in research that is shaping the future of TSC care.
