Charcot–Marie–Tooth disease

Overview

Charcot–Marie–Tooth disease (CMT) is a group of inherited neurological disorders that affect the peripheral nerves, the nerves outside the brain and spinal cord. Also known as hereditary motor and sensory neuropathy (HMSN), CMT causes progressive muscle weakness and wasting, primarily in the feet, lower legs, hands, and forearms. It is one of the most common inherited nerve disorders, affecting about 1 in 2,500 people worldwide. While CMT is typically not life-threatening, it can significantly impact mobility and quality of life.

Causes

CMT is caused by genetic mutations that affect the structure and function of peripheral nerves or the myelin sheath that surrounds them. It can be inherited in several patterns:

• Autosomal dominant: The most common form, where only one copy of the defective gene is needed

• Autosomal recessive: Requires two copies of the faulty gene (one from each parent)

• X-linked: Affects males more severely and is inherited through the mother

There are many subtypes of CMT based on the gene involved and the pattern of inheritance. The two major types are:

• CMT1: Caused by defects in the myelin sheath (demyelinating form)

• CMT2: Caused by defects in the nerve axon itself (axonal form)

Symptoms

Symptoms of Charcot–Marie–Tooth disease usually begin in adolescence or early adulthood, although onset and severity can vary. Common signs and symptoms include:

• Muscle weakness: Especially in the lower legs and feet, leading to foot drop and difficulty walking

• Muscle atrophy: Wasting of calf muscles, often giving the lower legs a “stork-like” appearance

• High foot arches (pes cavus) or flat feet

• Hammertoes: Contractures of the toes

• Loss of sensation: In the feet, legs, hands, or arms

• Difficulty with balance and coordination

• Hand weakness: Difficulty with fine motor tasks like buttoning clothes or writing

• Tingling or burning sensations: In some cases

Diagnosis

Diagnosis of CMT is based on clinical symptoms, family history, and diagnostic testing. Steps include:

• Neurological examination: To assess muscle strength, reflexes, and sensation

• Nerve conduction studies (NCS): Measure the speed and strength of electrical signals in peripheral nerves

• Electromyography (EMG): Evaluates muscle activity and detects nerve damage

• Genetic testing: To identify mutations associated with different CMT subtypes

• Nerve biopsy: Rarely used today, but may be performed in uncertain cases

Treatment

There is currently no cure for Charcot–Marie–Tooth disease, but supportive therapies can manage symptoms and improve function. Treatment typically involves a multidisciplinary approach:

• Physical therapy: Exercises to strengthen muscles, improve flexibility, and prevent contractures

• Occupational therapy: To assist with daily activities and hand function

• Orthotic devices: Braces, ankle-foot orthoses (AFOs), and custom footwear to support mobility

• Pain management: Medications for nerve pain, such as gabapentin or pregabalin

• Surgical interventions: For severe foot deformities or joint instability

• Genetic counseling: To inform affected individuals and their families about inheritance and family planning

Prognosis

The prognosis for individuals with Charcot–Marie–Tooth disease is generally good in terms of life expectancy, as the condition is not fatal. However, the degree of physical disability can vary. Many people remain ambulatory throughout life, while others may require mobility aids. The progression is usually slow, and symptoms can be managed with therapy and assistive devices. Early intervention and a personalized care plan can significantly enhance independence and quality of life.