Tuberous Sclerosis Complex

Tuberous Sclerosis Complex

Tuberous Sclerosis Complex (TSC) is an inherited genetic condition that affects different parts of the body in both children and adults. It causes non-cancerous (benign) tumours to grow in the brain and other vital organs such as the kidneys, heart, eyes, lungs, and skin.

Genetic Causes

TSC is caused by mutations in one of two genes: TSC1 (which produces a protein called hamartin) or TSC2 (which produces tuberin). These proteins work together to regulate cell growth and division. When either gene is mutated, cells can grow and divide uncontrollably, leading to the formation of benign tumours throughout the body.

TSC is an autosomal dominant condition — meaning only one copy of the mutated gene is sufficient to cause the condition. About one-third of TSC cases are inherited from a parent with TSC; the remaining two-thirds arise from new (de novo) mutations.

Associated Health Concerns

• Brain — cortical tubers, subependymal nodules, and subependymal giant cell astrocytomas (SEGAs); associated with epilepsy (in up to 90% of individuals), intellectual disability, autism spectrum disorder, and behavioural challenges

• Kidneys — angiomyolipomas (benign tumours) and renal cysts; can cause kidney failure in severe cases

• Lungs — lymphangioleiomyomatosis (LAM), primarily in women of childbearing age

• Heart — cardiac rhabdomyomas, usually present at birth and often regress spontaneously

• Skin — ash-leaf spots, facial angiofibromas, shagreen patches, and ungual fibromas

• Eyes — retinal hamartomas

Why Is Genetic Counselling Important?

“Genetic conditions might not have a cure, but genetic counselling and genetic testing is often the crucial first step to appropriate and vital recommendations for healthcare management and/or treatment for individuals with a genetic condition.” — Pooja Ramchandran, India’s pioneering genetic counsellor