Tuberous sclerosis

Tuberous sclerosis, also tuberous sclerosis complex (abbreviated TSC), is an autosomal dominant syndrome associated with an increased risk of hamartomas and some risk increase for malignant tumours.

Micrograph showing a renal angiomyolipoma, as may be seen in tuberous sclerosis. H&E stain. (WC/KGH)

Historically described as:

1. Epilepsy.
2. Mental retardation.
3. Adenoma sebaceum (angiofibromas).

General

• Autosomal dominant with variable penetrance.
• Majority (60-70%) are de novo mutations.
• May be treated with a mTOR inhibitor, e.g. everolimus.

Associations

Pathologic:

• Renal angiomyolipoma.
  • Represent approximately 85% of renal lesions in individuals with TSC.
• Cardiac rhabdomyoma.
• Lymphangiomyomatosis.
  • Seen in ~1/3 of females with TSC in one series.
• Subependymal giant cell astrocytoma (SEGA).
• Renal cysts.
  • Seen in ~45% of individuals with TSC in one series, no gender bias.
• Tuberous sclerosis-associated renal cell carcinoma - an evolving entity.

Note:

• The same genes (TSC1, TSC2) are implicated in PEComas.
• Renal lesions are seen in ~60% of patients.

Mnemonic SALSA HEART:

• Shagreen patches.
  • Shagreen patch = connective-tissue nevus composed of collagen, i.e. collagenoma.
• Ash Leaf spots.
• SEGA.
• Angiofibroma.
• Hamartomas.
• Epilepsy.
• Angiomyolipoma.
• Rhabdomyoma.
• Tubers.

Genes

• TSC1.
• TSC2.
  • Some evidence to suggest it is more often implicated in malignant tumours (than TSC1).
  • TSC2 mutations have a higher prevalence (than TSC1 mutations) and are considered more aggressive.

Notes:

• The proteins (hamartin and tuberin) are expressed in a wide variety of tissues.

Incidence

~1 in 10,000 population.

See also

• Adrenal gland.
• Kidney tumours.
• Neurocutaneous syndromes.
• PEComa.