Neurology - tuberous sclerosis

Question 1

What is tuberous sclerosis?

Answer 1

A genetic condition that causes features in multiple systems

Characteristic feature is the development of many hamartomas in different parts of the body

Question 2

What are hamartomas?

Answer 2

Benign neoplastic growths of the tissue that they originate from. Commonly affect:

• Skin
• Brain
• Lungs
• Heart
• Kidneys
• Eyes

They cause problems based on the tissue they occur in

Question 3

What are the mutations seen in tuberous sclerosis?

Answer 3

Tuberous sclerosis is caused by mutations in one of two genes:

• TSC1 gene on chromosome 9, which codes for hamartin
• TSC2 gene on chromosome 16, which codes for tuberin

Question 4

What do hamartin and tuberin do? What is the effect of mutation in the genes encoding these?

Answer 4

Hamartin and tuberin interact with each other to control the size and growth of cells.

Abnormalities in one of these proteins leads to abnormal cell size and growth.

Question 5

Classical skin features seen in tuberous sclerosis

Answer 5

Ash leaf spots are depigmented areas of skin shaped like an ash leaf

Shagreen patches are thickened, dimpled, pigmented patches of skin

Angiofibromas are small skin coloured or pigmented papules that occur over the nose and cheeks

Subungual fibromata are fibromas growing from the nail bed. They are usually circular painless lumps that grow slowly and displace the nail

Cafe-au-lait spots are light brown “coffee and milk” coloured flat pigmented lesions on the skin

Poliosis is an isolated patch of white hair on the head, eyebrows, eyelashes or beard

Question 6

What are the neurological features of tuberous sclerosis?

Answer 6

Epilepsy

Learning disability and developmental delay

Question 7

Other features of tuberous sclerosis

Answer 7

Rhabdomyomas in the heart

Gliomas (tumours of the brain and spinal cord)

Polycystic kidneys

Lymphangioleiomyomatosis (abnormal growth in smooth muscle cells, often affecting the lungs) - multiple lung cysts

Retinal hamartomas

Question 8

What is the classical presentation of someone with tuberous sclerosis?

Answer 8

A child presenting with epilepsy found to have skin features of tuberous sclerosis.

It can also present in adulthood.

Question 9

Management of tuberous sclerosis

Answer 9

Management is supportive with monitoring and treating complications such as epilepsy.

There is no treatment for the underlying gene defect.