RED PTS

Question 1

What is Charcot-Marie-Tooth disease?

Answer 1

group of inherited diseases that affects the peripheral motor and sensory nerves.

There are various types of Charcot-Marie-Tooth with different genetic mutations and different pathophysiology. They cause dysfunction in the myelin or the axons.

Question 2

Most common forms of CMT

Answer 2

CMT1 and CMT2, both of which are autosomal dominant diseases.

Question 3

What is CMT1 caused by?

Answer 3

caused by mutations in the PMP22 and MPZ genes, which encode proteins that are part of the myelin sheath made by the Schwann cells. Loss of myelin slows down transmission of electrical impulses through the nerves.

Question 4

Over time what happens in CMT1

Answer 4

Over time, Schwann cells try to replace the lost myelin. As a result, under a microscope, there’s often onion bulb formation - the axon is surrounded by layers of new myelin with underlying damaged layers of myelin.

Question 5

What happens in CMT2?

Answer 5

CMT2 is caused by mutations in the MFN2 gene which encodes a protein called Mitofusin-2 which is expressed in neuronal mitochondria. When the protein is defective, mitochondrial function is disrupted leading to neuronal death.

Question 6

Regardless of the part of the neurone thats affected, what happens to the signals?

Answer 6

signals fail to reach their target tissues, and this can affect both sensory and motor peripheral neurones.

Question 7

What happens in both CMT1 and CMT2?

Answer 7

when motor neurones are affected, muscles begin to atrophy. When sensory nerves are affected, it first affects the feet and toes first as those are the neurones with the longest axons, and are therefore most sensitive to damage.

Question 8

When do symptoms usually start to appear?

Answer 8

Symptoms usually start to appear before the age of 10 years but the onset of symptoms can be delayed until 40 or later.

Question 9

Signs of CMT

Answer 9

• Pes cavus: high foot arches
• Hammer toes: the middle joint of a toe bends upwards
• Distal muscle wasting causing inverted champagne bottle legs
• Hand and arm muscle wasting causing claw hand
• Thickened palpable nerves e.g. common peroneal

Question 10

Symptoms of CMT

Answer 10

• Weakness in the lower legs, particularly loss ofankle dorsiflexion
  
  • Foot drop
  • High-stepped gait
• Weakness in the hands
• Reduced tendon reflexes
• Reduced muscle tone
• Peripheral sensory loss
• Tingling and burning sensations in the hands and feet
• May be neuropathic pain

Question 11

Investigations for CMT

Answer 11

• Nerve conduction studies: measures ability of nerves to conduct impulses, conduction speed will be lowered.
• Neurologistsandgeneticiststo make the diagnosis: look for mutations

Question 12

DDs for CMT

Answer 12

• Diabetic neuropathy
• Chronic inflammatory demyelinating polyneuropathy
• Acquired peripheral neuropathy
• Hereditary spastic paraplegia
• Spinocerebellar degeneration

Question 13

Supportive management of CMT

Answer 13

• Physiotherapiststo maintain muscle strength and joint range of motion
• Occupational therapiststo assist with activities of living
• Podiatriststo help with foot symptoms and suggest insoles and other orthoses to improve symptoms
• Orthopaedic surgeonsto correct disabling joint deformities

Question 14

Complications of CMT

Answer 14

• Osteoarthritis
• Pain

Question 15

Prognosis of CMT

Answer 15

• Quality of life is good
• Total incapacity is rare

Question 16

Causes of peripheral neuropathy

Answer 16

• A–Alcohol
• B–B12 deficiency
• C–Cancer andChronic Kidney Disease
• D–Diabetes andDrugs (e.g.isoniazid,amiodaroneandcisplatin)
• E–Every vasculitis