Tuberous Sclerosis Complex (TSC) is a rare genetic disorder characterized by the growth of non-cancerous tumors in various organs throughout the body. These growths can affect the brain, kidneys, heart, eyes, lungs, and skin, leading to a wide range of symptoms. TSC is a lifelong condition, and its severity can vary significantly among affected individuals, even within the same family.
The Genetic Foundation of Tuberous Sclerosis
Tuberous Sclerosis Complex arises from mutations in either the TSC1 or TSC2 genes. The TSC1 gene is located on chromosome 9q34 and is responsible for producing a protein called hamartin. Similarly, the TSC2 gene, found on chromosome 16p13.3, provides instructions for creating the tuberin protein.
Both hamartin and tuberin normally work together as a complex to regulate cell growth and division. They function as tumor suppressors by interfering with the activity of another protein called mTOR, which plays a significant role in cell development. When a mutation occurs in either TSC1 or TSC2, this regulatory complex is disrupted, leading to uncontrolled cell proliferation. This uncontrolled growth results in the formation of the non-cancerous tumors in individuals with TSC.
Modes of Inheritance and Risk
Tuberous Sclerosis Complex is inherited in an autosomal dominant pattern, meaning one copy of the mutated TSC1 or TSC2 gene is necessary for an individual to develop the condition. This inheritance pattern affects males and females equally. The condition can manifest in two primary ways.
One way TSC can arise is through inheritance from an affected parent. If a parent carries a mutated TSC1 or TSC2 gene, there is a 50% chance with each pregnancy that their child will inherit the mutated gene and develop TSC. The symptoms and their severity can vary widely even within the same family, a phenomenon known as variable expressivity.
Approximately two-thirds of TSC cases result from a spontaneous, or de novo, mutation. In these instances, the genetic mutation occurs for the first time in an individual, meaning neither parent carries the altered gene. This explains why an individual can be diagnosed with TSC even without any family history of the condition.
Genetic Counseling and Family Planning
Genetic counseling offers valuable guidance for individuals and families navigating the complexities of Tuberous Sclerosis Complex. Genetic counselors provide comprehensive information about inheritance patterns, assess individual risk, and discuss various reproductive options. This support helps families make informed decisions tailored to their unique circumstances.
Genetic testing aids in diagnosis, risk assessment, and family planning. Diagnostic testing can confirm a TSC diagnosis in individuals presenting with symptoms. For those without symptoms but who are at risk, such as children of an affected parent, predictive testing can determine if they have inherited the mutated gene.
Prenatal testing can be performed during pregnancy to assess whether a fetus has inherited the TSC mutation. For couples undergoing in vitro fertilization (IVF), preimplantation genetic diagnosis (PGD) offers an option to screen embryos for the mutation before implantation. Informed decision-making and psychological support are available to help families cope with a TSC diagnosis.