Neuro - Tuberous Sclerosis, Neurofibromatosis and Charcot-Marie-Tooth

Question 1

What is tuberous sclerosis? Name the two mutations responsible for the condition

Answer 1

• Autosomal dominant condition causing developing of hamartomas (benign neoplastic growths of the tissue they originate from
• Usually affect skin, brain, lungs, heart, kidneys, eyes

Genes involved

-TSC1, chromosome 9: codes for hamartin -

TSC2, chromosome 16: codes for tuberin

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

Question 2

What are important signs to look for in a patient with tuberous sclerosis?

Answer 2

• Ash leafs spots: depigmented areas of skin that look like an ash leaf
• Shagreen patches: thickened, dimpled patches of skin
• Angiofibromas: small skill coloured or pigmented papeles on nose/cheeks
• Subungal/periungal fibromata: fibromas growing from nail bed - circular and painless and slowly displace the nail
• Cafe’ au lait spots: pigmented lesions on skin
• Poliosis: isolated patch of white hair in the head, eyebrows, eyelashes or beard

Question 3

TS: What is this?

Answer 3

-Ash leafs spots: depigmented areas of skin that look like an ash leaf

Question 4

TS: What is this?

Answer 4

-Subungal/periungal fibromata: fibromas growing from nail bed - circular and painless and slowly displace the nail

Question 5

TS: What is this?

Answer 5

-Shagreen patches: thickened, dimpled patches of skin

Question 6

TS: What are these?

Answer 6

-Angiofibromas: small skill coloured or pigmented papeles on nose/cheeks

Question 7

What is this?

Answer 7

Poliosis: isolated patch of white hair in the head, eyebrows, eyelashes or beard

Question 8

What are these?

Answer 8

-Cafe’ au lait spots: pigmented lesions on skin

Question 9

What neurological features are present in tuberous sclerosis?

Answer 9

• Epilepsy
• Learning disability and developmental delay

Question 10

What other features can be present in tuberous sclerosis?

Answer 10

• Rhabdomyomas in heart
• Gliomas
• Polycystic kidneys
• Retinal hamartomas
• Lymphangioleimyomatosis: abnormal growth in SM cells, usually affecting lungs

Question 11

What is the management for tuberous sclerosis?

Answer 11

• No cure or treatment
• Monitor and treat underlying complications, eg epilepsy

Question 12

What is neurofibromatosis? Name the types and genes involved

Answer 12

-Autosomal dominant condition that causes nerve tumours (neuromas) to develop throughout the nervous system. -Tumours are benign but cause neurological and structural problems.

Types

• type I: most common, associated with a tumour suppressor protein (neurofibromin) on chromosome 17
• type II: associated with protein (merlin) on chromosome 22

Question 13

NFT1: name some criteria which are used for diagnosis

Answer 13

Need at least 2 of 7 to make diagnosis (CRABBING)

• C: cafe-au-lait spots
• R: relative with NF1
• A: axillary or inguinal freckles
• BB: bone dysplasia eg bowing of long bone or sphenoid wing dysplasia
• I: iris hamartomas (lisch nodules)
• N: Neurofibromas
• G: glioma of optic nerve

Question 14

What are these these?

Answer 14

-GIioma of optic nerve

Question 15

NF: What is this?

Answer 15

Iris hamartomas

Question 16

What is neurofibromatosis type II? Name the predominant features and management

Answer 16

• Problems with merlin protein (chromosome 22), which codes for a tumour suppressor protein especially important in Schwann cells
• Leads to development of schwannomas
• Associated with bilateral acoustic neuromas (hearing loss, tinnitus, balance issues)
• Management is based on resection of accessible tumours

Question 17

Name some complications of NF

Answer 17

• Migraines
• Epilepsy
• Renal artery stenosis: HTN
• Scoliosis
• Vision loss (2nd to glioma)
• Malignant Peripheral nerve sheath tumours
• Gastrointestinal stromal tumour
• Brain tumour

Question 18

What is Charcot-Marie-Tooth?

Answer 18

• Autosomal dominant (majority of cases) disease that affects the peripheral motor and sensory nerves. Most cases are due to a dysfunction in the myelin or axons
• Sx usually appear by age 10 but onset can be delayed until 40 or later

Question 19

Describe some classical features of CMT

Answer 19

• High foot arches (pes cavus)
• Distal muscle wasting (inverted champagne bottle legs) -Weakness in lower legs and loss of ankle dorsiflexion -Weakness in hands
• Reduced tendon reflexes
• Reduced muscle tone
• Peripheral sensory loss

Question 20

How do you manage a pt with CMT?

Answer 20

• Refer to neurologist and geneticist for diagnosis
• PT: maintain strength and joint range of motion
• OT: help with activities of daily living
• Podiatrist
• Orthopods: correct disabling joints

Question 21

Name some causes of peripheral neuropathy

Answer 21

• A: alcohol
• B: b12 deficiency
• C: cancer and CKD
• D: diabetes and drugs (isoniazid, amiodarone and cisplatin)
• E: every vasculitis