Synopsis
Recognise inherited length-dependent motor and sensory neuropathy, confirm the neurophysiological and molecular subtype without indiscriminate genetic testing, and prevent falls, pressure injury, deformity and avoidable drug toxicity.
- Charcot-Marie-Tooth disease is a group of inherited motor and sensory neuropathies, typically causing slowly progressive length-dependent distal weakness, wasting, sensory loss and depressed reflexes.
- Foot drop, frequent ankle sprains, tripping, difficulty heel walking, pes cavus, hammer toes and thin lower legs are common early clues; hand weakness often emerges later.
- CMT1 is predominantly demyelinating with uniformly slow nerve conduction, CMT2 is predominantly axonal with relatively preserved velocities and reduced amplitudes, and intermediate forms overlap.
- PMP22 duplication causes the common autosomal-dominant CMT1A, while PMP22 deletion causes hereditary neuropathy with liability to pressure palsies, a related but distinct phenotype.
- Inheritance may be autosomal dominant, recessive, X linked or mitochondrial, so male-to-male transmission, skipped generations and maternal patterns can direct genomic testing.
- Sensory symptoms are often milder than motor disability but loss of pain and proprioception increases ulcer, burn, imbalance and injury risk.
- Tremor, scoliosis, hearing impairment, hip dysplasia, sleep-disordered breathing or diaphragmatic weakness occur in selected genotypes rather than every patient.
- Nerve-conduction studies establish a hereditary demyelinating, axonal or intermediate pattern and help distinguish uniform inherited slowing from patchy acquired demyelination.
- Genetic testing should follow phenotype, pedigree and neurophysiology through the NHS Genomic Test Directory, beginning with high-yield copy-number testing when appropriate.
- There is no universal disease-modifying medicine; ankle-foot orthoses, targeted exercise, foot care, occupational adaptation, pain treatment and selected orthopaedic surgery preserve function.
Key red flags
Weakness progressing over days or weeks, marked asymmetry, proximal predominance or new sphincter and bulbar features requires urgent search for a superimposed disorder.
Investigation priorities
Classify demyelinating, axonal or intermediate inherited neuropathy and assess uniformity.
Management branches
Slow distal weakness, cavus feet or a family history suggests Charcot-Marie-Tooth disease.
- Map motor, reflex and sensory findings in all limbs, inspect feet and spine, and ask about childhood milestones, falls, hearing, breathing and relatives.
- Build a three-generation pedigree including ages and severity, while explaining that absence of known affected relatives cannot exclude inherited disease.
- Refer for neuromuscular assessment and nerve conduction before broad genomic testing, screening acquired contributors only where presentation supports them.
Key medicines
AmitriptylineFor neuropathic pain, start at a low nightly oral dose such as 10 mg and titrate cautiously using the current BNF and local pathway.Anticholinergic effects, sedation, falls, postural hypotension, conduction disease and overdose toxicity require review, particularly where balance is already impaired.
GabapentinUse gradual oral titration under the current BNF with kidney-dose adjustment and a planned trial endpoint based on function and pain relief.Dizziness, oedema, somnolence, misuse and respiratory depression with opioids can worsen gait safety; taper after sustained use rather than stopping abruptly.