What is Tuberous Sclerosis?
According to the National Institute of Neurological Disorders and Stroke, Tuberous Sclerosis (also known as Tuberous Sclerosis Complex, TSC) is “a rare, multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin."
This genetic disease, discovered in 1880, is also known as Bourneville’s Disease and Epilola. TSC is an incurable genetic disorder with a wide range of signs, symptoms and effects. Manifestations of these vary from individual to individual. Mortality is usually due to brain tumors and kidney failure. Signs and symptoms of TSC include:
- cortical tubers (malformed tissue),
- benign growths (facial angiofibroma and subependymal nodules)
- cancerous hamartoblastomas (rare)
- skin abnormalities
- developmental delay
- behavioral problems
- mental retardation
- brain tumors
- Kidney problems (angiomyolipomas, cysts),
Tuberous Sclerosis Genetics
Tuberous sclerosis has an autosomal dominant pattern of inheritance. This implies that only one copy of a gene is damaged for the disease to be expressed (these are called dominant conditions because the mutation in one copy of the gene “dominates" over the other copy, causing the condition and its symptoms). Also, autosomal dominant inheritance means that the mutated gene is passed on to a child from one parent not both. If this is the case each child has a 50% chance of inheriting the disorder. Spontaneous mutations also causes the disease to appear in children of parents who do not carry the affected genes.
Genes causing the disease are still under investigation but so far two distinct causative genes have been discovered. These are known as the TSC1 and TSC2 genes. The TSC1 gene codes for a protein called hamartin and TSC2 codes for a protein called tuberin. Both tuberin and harmatin are tumor growth suppressors (they regulate cell growth and proliferation). Thus, mutations in these genes can trigger the formation of tumors.
Tuberous Sclerosis Gene on Chromosome 16
The TSC2 gene (also called the tuberin gene) is located on chromosome 16 while the TSC1 gene is located on chromosome 9. The Tuberous Sclerosis gene on chromosome 16 is around 50 kb in size and consists of 41 exons (exons are the coding regions of a gene). Exons 25 and 31 are alternatively spliced. The TSC2 gene shows many polymorphic variants in its coding region. More than 800 mutations have been identified in people affected by TSC . Approximately 60% of TSC2 mutations are small deletions (absence of a segment of DNA), insertions (segment of DNA is inserted into a gene), and splice site mutations.
Are There any Treatment Options for TSC?
At this point of time the TSC disease is incurable. The disease can be managed but not cured. Symptoms can be treated accordingly. Drugs for epilepsy can be used to prevent seizures while other drugs may be used for behavioral problems. Surgery is used for treatment of skin tumors.
Identification and characterization of the tuberous sclerosis gene on chromosome 16.
New developments in the neurobiology of the tuberous sclerosis complex. Neurology. 1999 Oct 22;53(7):1384-90.
Tuberous Sclerosis Fact Sheet (https://www.ninds.nih.gov/disorders/tuberous_sclerosis/detail_tuberous_sclerosis.htm)
Image credit: https://ghr.nlm.nih.gov/handbook/illustrations/autodominant (nih.gov)