Makindo Medical Notes

Related Subjects: |Neurological History taking

Age of onset is variable according to subtype, penetrance, familial phenotype, and ascertainment bias. Typically, CMT manifests in childhood or early adulthood.

About

• Charcot-Marie-Tooth (CMT) disease is a length-dependent peripheral sensory and motor neuropathy.
• Also called hereditary sensorimotor neuropathy (HSMN), CMT affects both motor and sensory nerves.
• Motor loss tends to predominate over sensory loss, although sensory impairment may be subclinical or subtle.

Epidemiology

• Prevalence: approximately 40 per 100,000 (or 1 in 2,500 individuals).
• More common in males than females.
• Less common in African American populations.

Aetiology

• Most cases are inherited in an autosomal dominant (AD) manner, though autosomal recessive (AR) and X-linked recessive (XLR) forms also exist.
• Myelin-based forms are most common, though some forms exhibit axonal degeneration.
• A common genetic mutation on chromosome 17 affects the PMP22 gene, which encodes a critical myelin protein.
• More than 50 different genetic mutations can cause CMT.

Associations

• Retinitis pigmentosa (seen in CMT Type 7).

Clinical Presentation

• Glove-and-stocking pattern of sensory loss, with distal muscle wasting.
• Claw hands, muscle cramps, and later onset of sensory symptoms.
• Hypertrophy of proximal muscles, leading to the "inverted champagne bottle" appearance in the legs.
• Thickened nerves may be palpable, especially in the ulnar and common peroneal nerves.
• Pes cavus (high arched feet) or pes planus (flat feet) is commonly observed in early adulthood.
• Foot drop and absent ankle jerks are common, as is "stocking" sensory loss.
• Patients often recall difficulty running or participating in sports during childhood.

Image:

The foot of a person with Charcot-Marie-Tooth disease. The lack of muscle, a high arch, and claw toes are typical signs of this genetic disease.

Different Forms of CMT

Investigations

• DNA analysis: Genetic testing is available for many forms of CMT to identify specific mutations.
• Nerve conduction studies: Most commonly show slowed conduction in demyelinating forms like CMT Type I.
• Electromyography (EMG): Used to assess muscle electrical activity.
• Lumbar puncture and CSF analysis: Elevated CSF protein levels, especially in CMT Type III.

Worsened by:

• Emotional stress.
• Periods of prolonged immobility.
• Pregnancy (symptoms may worsen during pregnancy due to increased progesterone).
• Certain medications, such as vincristine, amiodarone, and colchicine.

Management

• Life expectancy is generally normal, although some patients may develop sleep apnoea.
• Genetic counseling is recommended, especially for families with known CMT inheritance.
• Foot care is critical: patients should avoid walking barefoot and check for unnoticed injuries due to sensory loss.
• In severe cases, a wheelchair may be required for mobility.

References

• Online presentation on CMT