Hereditary Motor Sensory Neuropathies

Imaging Gallery

Click to expand

Click to expand

Click to expand

Click to expand

Definition: Hereditary Motor Sensory Neuropathies (HMSN), also known as Charcot-Marie-Tooth (CMT) disease, are a group of inherited peripheral neuropathies characterized by progressive distal muscle weakness and sensory loss.

Epidemiology:

• Incidence: 1 in 2500 (Most common inherited neuropathy).
• CMT1A: 50% of all CMT cases.
• Inheritance: Mostly Autosomal Dominant.

Historical Note: Named after Jean-Martin Charcot, Pierre Marie (France), and Howard Henry Tooth (UK) who independently described the condition in 1886.

Genetic Basis of HMSN/CMT:

Key Genetic Points:

• CMT1A (50%): PMP22 gene duplication (Chromosome 17). Most common cause.
• CMT1B: MPZ (Myelin Protein Zero) mutation. Demyelinating.
• CMT2A: MFN2 (Mitofusin 2) mutation. Axonal transport defect.
• CMTX: Connexin 32 mutation. X-linked inheritance.

Genetic Testing:

• First-line: PMP22 duplication/deletion analysis (detects 70% of CMT1).
• Second-line: Targeted gene panels or whole exome sequencing.
• Prenatal testing available for known familial mutations.

Cellular and Molecular Mechanisms:

CMT pathophysiology depends on the specific genetic defect:

CMT1 (Demyelinating - 60% of cases):

• Schwann Cell Dysfunction: PMP22 or MPZ mutations disrupt myelin formation.
• Demyelination/Remyelination Cycles: Repeated attempts at remyelination create characteristic 'onion bulb' formation on nerve biopsy.
• Result: Slowed nerve conduction velocities (less than 38 m/s).
• Clinical Effect: Progressive distal weakness and sensory loss.

CMT2 (Axonal - 20% of cases):

• Axonal Degeneration: MFN2 mutations affect mitochondrial function and axonal transport.
• Wallerian Degeneration: Distal axon breakdown without primary demyelination.
• Result: Normal conduction velocities but reduced amplitude.
• Clinical Effect: Similar weakness pattern, often later onset.

Mechanism of Cavovarus Foot Deformity:

The characteristic foot deformity results from selective muscle weakness:

1. Peroneus Brevis: Weakens first (primary evertor of hindfoot).
2. Tibialis Posterior: Relatively preserved. Unopposed inversion pulls hindfoot into varus.
3. Peroneus Longus: Relatively preserved. Plantarflexes 1st metatarsal creating forefoot equinus.
4. Intrinsic Muscles: Early weakness. Long flexors/extensors become dominant causing claw toes.
5. Plantar Fascia: Secondary contracture contributes to arch elevation.

Net Result: Cavovarus foot (High arch + Hindfoot Varus + Claw toes + Forefoot adduction).

Progression Pattern:

• Distal-to-proximal weakness ('dying back' neuropathy).
• Lower limbs affected before upper limbs.
• Sensory loss follows similar pattern.
• Deformity progresses throughout growth and into adulthood.

Key Anatomy: Understanding the relevant anatomy is crucial for diagnosis and management. The structures involved include the osseous architecture and surrounding soft tissues.

Pathomechanics: The injury mechanism often involves specific loading patterns that disrupt the structural integrity.

History:

• Family History: Autosomal dominant (often affected parent).
• Onset: Usually childhood/adolescence.
• Symptoms: Difficulty walking, frequent ankle sprains, foot drop, clumsiness.

Physical Examination:

• Inspection:
  • 'Stork legs' (Distal wasting, Normal proximal).
  • Cavovarus foot (High arch, Hindfoot varus).
  • Claw toes.
  • Calluses (Metatarsal heads, Lateral foot).
• Motor:
  • Weak ankle dorsiflexion (Foot drop).
  • Weak eversion (Peroneus Brevis).
  • Weak toe extension/flexion (Intrinsics).
• Sensory: Glove-stocking sensory loss.
• Reflexes: Reduced/absent ankle jerks.
• Gait: Steppage gait (High stepping to clear foot).

Coleman Block Test:

1. Patient stands on a 2-3cm block.
2. Lateral foot on block. 1st ray (1st MT head) hangs off medially.
3. Observe Hindfoot: Does varus correct?
4. If Corrects: Varus is FOREFOOT-DRIVEN (1st ray plantarflexion). Surgery addresses 1st ray.
5. If Does Not Correct: Varus is FIXED/HINDFOOT. Surgery needs calcaneal osteotomy.

Diagnosis:

1. Clinical Examination: Often sufficient.
2. NCS/EMG:
   • CMT1: Slow conduction velocities (less than 38 m/s).
   • CMT2: Normal velocity, Reduced amplitude.
3. Genetic Testing: Confirms specific mutation (CMT1A = PMP22 duplication).
4. Nerve Biopsy: Rarely needed. 'Onion bulbs' in CMT1.

Orthopaedic Assessment:

1. Weight-Bearing X-rays: AP, Lateral foot. Assess arch height, Meary's angle.
2. Coleman Block Test: As above.
3. Spine X-ray: Screen for scoliosis.

After Osteotomies:

• NWB Cast 6-8 weeks.
• Transition to AFO or supportive footwear.
• Physiotherapy for ROM and strengthening.

After Tendon Transfers:

• Splint in corrected position 4-6 weeks.
• Gradual retraining of transferred muscles.

• Short-term: Good correction achievable.
• Long-term: Recurrence is common due to progressive nature of CMT.
• Function: Surgery improves stability, reduces pain, improves gait.

• Neuromuscular Clinics: MDT clinics at pediatric hospitals.
• Genetic Testing: Available through state genetics services (Medicare funded).
• NDIS: Supports orthotics, therapy, mobility aids.