Age of onset is variable according to subtype, penetrance,
familial phenotype, and ascertainment bias
About
- Length dependent peripheral sensory and motor neuropathy
- Also called Hereditary sensorimotor neuropathy (HSMN Type 1)
- Motor loss tends to predominate rather than sensory
- Sensory loss may be subclinical
Epidemiology
- Prevalence: 40 per 100,000 ( 1 in 2500)
- Males>Females
- Less common in African Americans
Aetiology
- Most are inherited as AD others AR and XLR
- Most forms are myelin based though some have axonal degeneration
- The gene on Chromosome 17 encodes a myelin protein PMP22
- More than 50 genes causing CMT have been identified
Associations
- Retinitis pigmentosia (CMT7)
Image: The foot of a person with Charcot-Marie-Tooth disease: The lack of muscle, a high arch, and claw toes are signs of this genetic disease.
Clinical
- Glove and stocking losses and distal muscle wasting
- Claw hands, cramps, sensory symptoms may come on later
- Hypertrophy of the proximal muscles - inverted champagne bottle
- May be palpable nerve thickening - ulnar and common peroneal
- Comes on age 10-30 with pes cavus (high arched feet)
- Some may have flat feet (Pes plannus)
- Distal muscle wasting of legs appear as "inverted champagne bottles"
- Foot drop and distal "stocking" sensory loss and absent ankle jerks
- Recall being bad at sports and difficulty running and a similar family history
Different forms
Type | Details |
Type I | Charcot-Marie-Tooth disease, peroneal muscular atrophy. Autosomal dominant. Weakness and atrophy affects primarily the peroneal and distal leg muscles. Foot drop and wasting distally + pes cavus. Absent ankle jerks. Nerve conduction velocities are slow |
Type II | Charcot-Marie-Tooth disease, peroneal muscular atrophy. As for Type 1 but weakness usually develops later in life. Patients have relatively normal nerve conduction velocities |
Type III | Hypertrophic interstitial neuropathy/ Dejerine-Sottas disease. Rare, Autosomal recessive. Progressive weakness and sensory loss. Enlarged palpable peripheral nerves. CSF protein > 10 g/L |
Investigations
- DNA analysis helpful for some forms of CMT
- Nerve conduction studies - see above most commonly slowed conduction
- Electromyography
- Lumbar puncture and CSF analysis - elevated protein with Type III
Worsened by
- Emotional stress
- Periods of prolonged immobility
- Pregnancy, Drugs
- Vincristine, amiodarone, Colchicine etc.
Management
- Life expectancy: normal. Some have sleep apnoea
- Pregnancy Disease exacerbation can occur in pregnancy, an effect that may be mediated by increased plasma progesterone
- Genetic counselling that disease may affect offspring
- Counsel that symptoms can worsen with pregnancy
- Good foot care and avoidance of walking barefoot and inspecting feet for injuries that are not felt.
- In severe cases wheelchair may be needed for mobilisation
References