Skip to content

Tuberous sclerosis

Videos

Notes

Nervous system

Pathology

Central nervous system disorders
Central and peripheral nervous system disorders
Peripheral nervous system disorders
Autonomic nervous system disorders
Nervous system pathology review

Assessments
Tuberous sclerosis

Flashcards

0 / 13 complete

Questions

1 / 2 complete
High Yield Notes
0 pages
Flashcards

Tuberous sclerosis

13 flashcards
Questions

USMLE® Step 1 style questions USMLE

2 questions
Preview

A 5-year-old child with intellectual disability is brought to the clinic by his parents due to progressive growth of facial lesions. His parents first noted it a few months ago and tried several over-the-counter creams with minimal improvement. Medical history is notable for seizures, hyperactivity, and mild cognitive dysfunction. Vitals are within normal limits. Physical examination reveals the facial lesions shown below:  


Reproduced from: Wikipedia    

Which of the following additional findings is most likely to be found on further examination of this patient?    

External References
Transcript

Tuberous sclerosis is a genetic condition that causes growths to form in various body organs. Most commonly affecting the brain, skin, kidneys, lungs, and eyes.

Normally, there are two genes called TSC1 and TSC2 that help control the growth and division of cells in the body.

TSC1 encodes the protein hamartin and TSC2 encodes the protein tuberin.

Both of these proteins, are tumor suppressors, meaning they help slow down cell growth and prevent tumors.

They do this by combining to form a hamartin-tuberin protein complex, which binds to and inhibits another protein called mechanistic target of rapamycin, or mTOR.

mTOR activity speeds up the cell cycle and increases cell proliferation mainly thanks to its effect on protein synthesis.

So when mTOR is switched off by the hamartin-tuberin protein complex, it slows growth and division of cells throughout the body.

Individuals with tuberous sclerosis have a mutation in either the gene TSC1 or TSC2, and these mutations have an autosomal dominant inheritance pattern.

The mutations lead to an altered hamartin-tuberin protein complex that’s unable to switch off mTOR.

Because of that, benign tumors and growths called hamartomas form throughout the body.

Hamartomas are kind of like tumors, but they’re made of a variety of cell types from the tissue where they arise, rather than a single cell type.

In fact, if we think of the tissue like a sheet of fabric, a hamartoma is like a knot in the sheet.

Benign tumors and hamartomas can form in any tissue, but the brain and the skin are usually affected the most, along with the kidneys, lungs and eyes.

On top of that the lifetime risk of cancer is increased in individuals with tuberous sclerosis.

That’s because the rapidly dividing cells can develop additional mutations that eventually make these growths expand beyond the basement membrane and invade neighboring tissues.

In the brain, the most common growths are glioneural hamartomas, also known as a cortical tubers. They arise from supportive glial cells as well as neurons.

Next most common are subependymal nodules, which are hamartomas that form under the ependyma, the thin membrane that lines the ventricles in the brain.

Individuals are also at an increased risk of developing a subependymal giant cell astrocytoma, or SEGA, which is a type of cancer that can arise from the subependymal nodules.

Summary
Tuberous sclerosis or tuberous sclerosis complex (TSC) is a rare multi-system genetic disease that causes benign tumors to grow in the brain and on other vital organs such as the kidneys, heart, eyes, lungs, and skin. A combination of symptoms may include seizures, intellectual disability, developmental delay, behavioral problems, skin abnormalities, lung and kidney disease. TSC is caused by a mutation of either of two genes, TSC1 and TSC2, which code for the proteins hamartin and tuberin, respectively. These proteins act as tumor growth suppressors which regulate cell proliferation and differentiation.
Sources
  1. "Robbins Basic Pathology" Elsevier (2017)
  2. "Harrison's Principles of Internal Medicine, Twentieth Edition (Vol.1 & Vol.2)" McGraw-Hill Education / Medical (2018)
  3. "Pathophysiology of Disease: An Introduction to Clinical Medicine 8E" McGraw-Hill Education / Medical (2018)
  4. "CURRENT Medical Diagnosis and Treatment 2020" McGraw-Hill Education / Medical (2019)
  5. "A clinical update on tuberous sclerosis complex‐associated neuropsychiatric disorders (TAND)" American Journal of Medical Genetics Part C: Seminars in Medical Genetics (2018)
  6. "Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors" Kidney International (2006)
  7. "Abnormal glycogen storage in tuberous sclerosis complex caused by impairment of mTORC1-dependent and -independent signaling pathways" Proceedings of the National Academy of Sciences (2019)
  8. "Tuberous Sclerosis Complex Diagnostic Criteria Update: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference" Pediatric Neurology (2013)