Overview
- Neurocutaneous syndrome with autosomal dominant inheritance pattern with the development of hamartomas and benign neoplasms.
Genetics
- Autosomal dominant inheritance pattern
- TSC1 mutation on chromosome 9
- TSC1 encodes for hamartin.
- TSC2 mutation on chromosome 16
- TSC2 encodes for tuberin.
Both hamartin and tuberin are involved in inhibition of the mechanistic Target of Rapamycin (mTOR) pathway (mTOR is also an important factor in the development of gliomas in
Neurofibromatosis, Type 1).
Clinical Manifestations:
- Hamartomas (firm, like "potatoes") of the CNS (cortex) and skin.
- Haphazardly arranged neurons.
- Facial angiofibromas (adenoma sebaceum)
- Ash-leaf spots (hypopigmentation), shagreen patches (leathery thickening patches), subungual fibromas
- Cardiac rhabdomyomas and mitral regurgitation
- Mental disability and seizures
- These are the key neurological impairments but the degree of cognitive dysfunction and the severity of seizure activity varies widely.
- The number of cortical tubers (hamartomas; nonenhancing MRI lesions) appears to be directly related to the severity of infantile spasms.
- Renal angiomyolipoma
- Subependymal giant cell astrocytomas (SEGAs) are nearly exclusively found in tuberous sclerosis.
- Note that Everolimus is an mTOR inhibitor and is used in the treatment of enlarging SEGAs.
- Cysts
- Candle Guttering Sign
- Note that the "candle gutterings" are sub-ependymal nodules found in tuberous sclerosis: they are smooth, round projections into the ventricles that look like drippings of wax along a candle.
- “December 27, 2010 e-Pearl of the Week: ‘Candle Guttering’ Sign in Tuberous Sclerosis | Neurology.” Accessed August 6, 2018. http://n.neurology.org/epearls/20101227.