Tuberous sclerosis

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Tuberous Sclerosis one of the Phakomatoses (Neurocutaneous Syndromes). It is a multi-system genetic disease that causes benign tumors (hamartomas) that affect the brain, and other visceral organs including the kidneys, heart, eyes, lungs, and skin. It is also known as Bourneville's Disease (named after Desire-Magloire Bourneville in 1880).


TS occurs in all ethnicities and races. The incidence is estimated to be between 10-16 cases per 100,000.

Clinical Presentation

A clinical triad is frequently seen and includes seizures, developmental delay, and facial angiofibromas (adenoma sebaceum). This is also pejoritavely known as "fits, zits and nitwits". 50% of patients will have developmental delay. 60-80% of patients will have hamartomas on the kidneys which may cause hematuria. 50% of patients will have rhabdomyomas on the heart. Greater than 95% of patients will have a dermatological sign which include:

  1. Facial angiofibromas (adenoma sebaceum)
  2. Ungual or subungual fibromas
  3. Hypomelanic macules - so-called ashleaf macules
  4. Forehead plaques
  5. Shagreen patches

50% of patients will also have a retinal hamartomas.


CT and MRI can reveal classic lesions seen in TSC which include subependymal nodules and cortical/subcortical tubers. The subependymal nodules are also known as "candle guttering" and appear along the ventricular margins. These may enlarge over time and are thought to give rise to Subependymal Giant Cell Astrocytomas (SEGAs). Cortical/subcortical tubers appear as nodular swellings on the cortical surface.




Tuberous sclerosis is a genetic disorder with an autosomal dominant pattern of inheritance, and penetrance is 100%.[7] Two thirds of TSC cases result from sporadic genetic mutations, not inheritance, but their offspring may inherit it from them. Current genetic tests have difficulty locating the mutation in approximately 20% of individuals diagnosed with the disease. So far it has been mapped to two genetic loci, TSC1 and TSC2.

TSC1 encodes for the protein hamartin, is located on chromosome 9 q34 and was discovered in 1997.[8] TSC2 encodes for the protein tuberin, is located on chromosome 16 p13.3 and was discovered in 1993.[9] TSC2 is contiguous with PKD1, the gene involved in one form of polycystic kidney disease (PKD). Gross deletions affecting both genes may account for the 2% of individuals with TSC who also develop PKD in childhood.[10] TSC2 has been associated with a more severe form of TSC.[11] However, the difference is subtle and cannot be used to identify the mutation clinically. Estimates of the proportion of TSC caused by TSC2 range from 55% to 80-90%.[12]

TSC1 and TSC2 are both tumor suppressor genes that function according to Knudson's "two hit" hypothesis. That is, a second random mutation must occur before a tumor can develop. This explains why, despite its 100 percent penetrance, TSC has wide expressivity.


Subependymal nodules are composed of abnormal, swollen glial cells and bizarre multinucleated cells which are indeterminate for glial or neuronal origin. There is no interposed neural tissue. These nodules have a tendency to calcify as the patient ages.


Generally, treatment is offered when a SEGA enlarges. This often results in neurologic symptoms including headaches, and signs of increased intracranial pressure as a consequence of hydrocephalus.

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