Charcot-Marie-Tooth Disease (CMT)

Charcot-Marie-Tooth Disease (CMT)

• CMT, also known as hereditary motor and sensory neuropathy (HMSN), is a progressive disorder affecting the peripheral nervous system.
• The condition impacts motor and sensory nerves, leading to muscle weakness, sensory loss, and foot deformities.

Patient Presentation

• An 18-year-old male reports difficulty walking, calf pain, fatigue, foot drop, and weakness, hindering his ability to play soccer.
• Symptoms include calf atrophy, pes cavus (high arches), decreased deep tendon reflexes, and sensory deficits in the L1 to L4 dermatome.
• The patient describes intermittent, deep, achy calf pain that lasts 10-30 minutes and is relieved by rest.

Symptoms and Clinical Presentation

• Calf atrophy indicates muscle dysfunction due to issues with the muscle or innervation.
• Pescavus, or high arches, is common in neurological conditions affecting sensory nerves in the foot.
• Sensory loss (inability to differentiate hot and cold) points to sensory nerve dysfunction.
• Decreased reflexes in the Achilles and patella regions suggests lower motor neuron involvement.

Diagnosis

• Electromyography (EMG) and nerve conduction studies assess electrical signal travel along nerves.
• DNA testing confirms diagnosis by identifying mutations in genes such as PMP22, MPZ (CMT Type 1), or MFN2 (CMT Type 2).
• Nerve biopsy reveals "onion bulb" formations from Schwann cell proliferation, indicating myelin sheath damage.

Genetic Causes and Types

• CMT is typically caused by mutations in genes coding for proteins involved in nerve myelination or axonal function.
• CMT Type 1, the most common form, results from mutations in PMP22 or MPZ genes, affecting myelin sheath production by Schwann cells.
• CMT Type 2 is caused by mutations in the MFN2 gene, leading to dysfunctional mitochondria and neuronal loss.

Pathophysiology of CMT

• Myelin dysfunction impairs rapid transmission of electrical signals along nerve axons.
• Schwann cells attempt to repair damaged myelin by proliferating and forming "onion bulb" structures.
• Axonal defects, such as MFN2 mutations, disrupt nerve cell function, leading to neuronal loss via apoptosis.

Clinical Features

• Early symptoms include tingling or numbness in extremities, particularly in the hands and feet.
• As the disease progresses, patients develop foot drop, muscle weakness in the legs, and calf muscle atrophy.
• Stork leg appearance, with calf muscle atrophy and unaffected thigh muscles, is a classic sign.
• Foot deformities, such as high arches (pes cavus) and hammer toes, are common.
• Gait abnormalities, including a high-step gait to compensate for foot drop, are often observed.

Treatment and Management

• Regular physical therapy helps strengthen muscles and improve mobility.
• Assistive devices such as crutches or wheelchairs may be needed as muscle weakness progresses.
• Orthotic support with special footwear and ankle-foot orthoses (AFOs) can improve foot position and gait.
• Surgical intervention may be necessary to correct foot deformities or manage severe joint contractures.

Prognosis

• CMT is a progressive disease with varying rates of progression.
• Symptoms often begin in childhood or adolescence, with increasing foot deformities and weakness.
• Life expectancy is usually normal with appropriate symptom management.

Key Takeaways

• CMT is a group of hereditary motor and sensory neuropathies affecting peripheral nerves.
• Diagnosis involves clinical evaluation, electromyography, nerve conduction studies, and genetic testing.
• Treatment focuses on improving mobility through physical therapy, assistive devices, and orthotics.
• CMT can cause stork leg appearance, high arches, hammer toes, and foot drop, with early sensory changes in the feet and hands.
• Onion bulb formation in Schwann cells and mitochondrial dysfunction in CMT Type 2 are critical diagnostic findings.