Table of Contents
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