Tuberous Sclerosis Complex

Main Features

  • Benign tumors of the brain, kidney, lung, heart and eyes.
  • One of the phakomatoses

Eye Findings

  • Retinal astrocytic hamartomas 34-75% of patients with TSC.
    • flat, translucent lesions, multinodular “mulberry” lesions, and transitional types.
    • usually non-progressive but can occasionally show subretinal fluid and progression.
    • Typically located along the arcades, adjacent to the optic nerve, or in the retinal periphery.
  • Retinal achromic patches 34%
    • hypopigmented areas similar to the hypomelanotic macules seen on the skin
    • Usually non-progressive and do not significantly affect vision
  • Refractive errors (myopia, hyperopia, and astigmatism),
  • Strabismus
  • Angiofibromas of the eyelids- rare
  • Coloboma- rare

Other Findings

  • Brain (leading cause of morbidity)
    • subependymal nodules
    • cortical tubers
    • subependymal giant cell astrocytomas
    • Seizures
    • neuropsychiatric disorders/ developmental delay
  • Cardiac
    • rhabdomyomas
    • arrhythmias
  • Renal (leading cause of mortality)
    • benign renal angiomyolipomas
    • epithelial cysts
    • oncocytoma
  • Lungs
    • lymphangioleiomyomatosis
    • multifocal micro odular pheumonocyte hyperplasia
  • Dermatologic
    • Angiofibromatosis
    • Shagreen patches

Etiology

  • Autosomal Dominant with near complete penetrance but variable expressivity due to Knudson's two-hit hypothesis
  • Mutations result in unregulated cell growth leading to hamartomas
  • Mutations in TSC1 (25%)
    • Encodes for gene hamartin- a tumor supressor gene
    • Chromosome 9q34
  • Mutations in TSC2 (75%)
    • Encodes for gene tuberin- a tumor supressor gene
  • Both genes inhibit the mammalian large of rapamycin (mTOR) pathway

Resources

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