Which are the causes of Tuberous Sclerosis?

Causes of Tuberous Sclerosis

Tuberous Sclerosis (TS), also known as tuberous sclerosis complex (TSC), is a rare genetic disorder that affects multiple organ systems in the body. It is characterized by the growth of noncancerous tumors, called hamartomas, in various organs, including the brain, heart, kidneys, lungs, and skin. The exact cause of tuberous sclerosis is related to genetic mutations, specifically in two genes: TSC1 and TSC2.

Genetic Mutations:

Tuberous sclerosis is primarily caused by mutations in the TSC1 and TSC2 genes. These genes provide instructions for producing proteins that regulate cell growth and division. In individuals with tuberous sclerosis, mutations in either the TSC1 or TSC2 gene disrupt the normal functioning of these proteins, leading to uncontrolled cell growth and the formation of hamartomas.

TSC1 Gene Mutations:

The TSC1 gene is located on chromosome 9 and encodes a protein called hamartin. Mutations in the TSC1 gene account for approximately 25% of tuberous sclerosis cases. When the TSC1 gene is mutated, it impairs the ability of hamartin to interact with other proteins involved in cell growth regulation, resulting in the development of hamartomas.

TSC2 Gene Mutations:

The TSC2 gene is located on chromosome 16 and encodes a protein called tuberin. Mutations in the TSC2 gene are responsible for about 75% of tuberous sclerosis cases. Similar to TSC1 mutations, TSC2 mutations disrupt the normal function of tuberin, leading to uncontrolled cell growth and the formation of hamartomas.

Autosomal Dominant Inheritance:

Tuberous sclerosis follows an autosomal dominant pattern of inheritance, which means that a person only needs to inherit a mutation in one copy of either the TSC1 or TSC2 gene to develop the disorder. In most cases, the mutation is not inherited from either parent but occurs spontaneously during the formation of reproductive cells or early embryonic development.

Mosaicism:

In some instances, tuberous sclerosis can occur due to mosaicism. Mosaicism refers to the presence of two or more genetically distinct cell populations within an individual. In mosaic tuberous sclerosis, the mutation arises after fertilization, resulting in some cells having the mutation while others do not. This can lead to variations in the severity and presentation of symptoms among affected individuals.

Other Genetic Factors:

While mutations in the TSC1 and TSC2 genes are the primary cause of tuberous sclerosis, other genetic factors may influence the severity and specific manifestations of the disorder. Modifier genes, which can enhance or suppress the effects of the TSC1 and TSC2 mutations, may play a role in determining the variability of symptoms observed in individuals with tuberous sclerosis.

Conclusion:

Tuberous sclerosis is a complex genetic disorder caused by mutations in the TSC1 and TSC2 genes. These mutations disrupt the normal regulation of cell growth and division, leading to the formation of hamartomas in various organs. The disorder follows an autosomal dominant pattern of inheritance, although many cases occur sporadically due to new mutations. Mosaicism and other genetic factors may contribute to the variability of symptoms observed in individuals with tuberous sclerosis.