Charcot Marie Tooth

Hereditary Motor Sensory Neuropathies I-III

 

Epidemiology

 

1: 3000

 

Definition

 

Group of inherited peripheral sensory & motor neuropathies

- includes Charcot Marie Tooth Disease

 

Classification

 

Hypertrophic vs Neuronal HMSN 

 

I   Hypertrophic CMT

II  Neuronal CMT

III Infantile Hypertrophic Neuropathy - Dejerine-Sottas

IV  Refsum's disease

 

Orthopaedic Complications

 

Cavovarus Foot

 

Claw Toe

 

Hip Dysplasia

 

10 % CMT

- muscle imbalance promotes femoral anteversion & valgus neck

- 2° acetabular dyplasia

 

Management

- as per usual

- NB care with sciatic nerve as more susceptible than normal

- usually bony surgery

 

Scoliosis 

 

50%

- management as per idiopathic

 

Hypertrophic CMT HSMN I

 

Definition

 

Demyelinating peripheral neuropathy

- repetitive demyelination & remyelination leads to nerve hypertrophy = Onion bulb

- more demyelinated fibres than myelinated

 

Characterised by

- demyelination

- areflexia

- decreased nerve conduction velocity

 

Aetiology

 

AD 

- triple dose of peripheral myelin protein 22 

- chromosomal linkage on chr 17 (17p11.2) 

- gene encodes periph myelin ptn 22

 

Histology 

 

Demyelination & fibrosis

- 'Onion-bulb' appearance

 

Clinical Features

 

Present in children / teens

 

Lower limbs more affected

 

Areflexia

 

Symmetrical distal muscle weakness and wasting

- weakness progresses to all muscles distal to knee

- develop high-stepping drop-foot gait

- inverted champagne bottle

 

Stork legs CMT Stork Legs CMT 2

 

Glove and stocking sensory loss

 

Cavo-varus

- initial mild cavus & toe clawing

- becomes rigid 

 

CMT Foot 1CMT Foot 2

 

Upper limb involvement 

- begins later 

- starts with intrinsic wasting

- mixed median and ulnar 

- then radially supplied muscles

 

CMT Hands 1CMT Hands 2

 

NCS

 

Motor nerve conduction velocities decreased by > 50%

 

Diagnosis

 

Nerve Biopsy

 

Genetic testing

- mutation in 17q11 or X-linked connexin 33

 

Neuronal CMT HSMN II

 

Differences

- axonal neuropathy without demyelination

- reflexes preserved 

- normal nerve conduction velocity

 

Aetiology

 

AD

- abnormality in spinal cord neurones

 

Histology 

- neuronal degeneration with preservation of myelin

 

Clinical Features

 

Present in teens / early adulthood

- less disabling than HSNM I

- upper limb involvement less severe than Type 1

 

Reflexes present 

 

Glove and stocking sensory loss only mild

 

More profound distal lower limb involvement than Type 1

- stork-leg appearance

- wasted distal thigh / leg muscles

- flail foot

- calcaneocavus deformity

 

CMT Stork LegsCMT Cavus

 

Investigations

 

Motor NCS normal

 

Infantile Hypertrophic Type III

 

Aetiology

 

Dejerine-Sottas disease

- AR (no normal gene for peripheral myelin ptn 22 present)

 

Pathology

 

Hypertrophic interstitial neuropathy

- histology shows segmental demyelination & marked nerve thickening with Perineural fibrosis

 

Clinical Features

 

Presents in infancy

- pes cavus & drop foot

- stocking-glove sensory loss

- significant spinal deformity

- confined to wheelchair by 30s

 

Investigations

 

Markedly slowed motor NCS

 

Refsum's disease Type IV

 

AR

- rare disease with Cranial Nerve involvement