Neurology · Hereditary Neuropathies
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Charcot-Marie-Tooth disease is a hereditary motor and sensory neuropathy most commonly caused by a duplication of the PMP22 gene.
Patients classically present with distal muscle weakness and atrophy of the lower extremities, often described as stork legs or inverted champagne bottle legs.
Physical examination reveals pes cavus (high arches) and hammer toes due to chronic muscle imbalance and weakness.
Neurological assessment typically demonstrates diminished or absent deep tendon reflexes and distal sensory loss in a stocking-glove distribution.
The disease follows an autosomal dominant inheritance pattern in the vast majority of cases.
Electromyography and nerve conduction studies show slowed nerve conduction velocities consistent with a demyelinating neuropathy.
Management is primarily supportive and focuses on physical therapy, orthopedic bracing (e.g., AFOs), and surgical correction of severe foot deformities.
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A 22-year-old male presents to the clinic for evaluation of chronic gait instability and frequent ankle sprains. He reports that his feet have always had a high arch and his toes are curled. On physical exam, he has atrophy of the distal lower extremities with a sharp transition to normal muscle bulk at the mid-calf, resembling an inverted champagne bottle. He has absent ankle jerks bilaterally and pes cavus deformities. Sensation to vibration and pinprick is decreased in a stocking-glove distribution.
What is the most likely diagnosis?
Charcot-Marie-Tooth disease
The patient's presentation of distal muscle atrophy, pes cavus, and absent reflexes is classic for Charcot-Marie-Tooth, which is tested via the constellation of physical findings (Bet 2, 3, and 4).
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Etiology / Epidemiology
Most common hereditary motor and sensory neuropathy; typically autosomal dominant inheritance.
Clinical Manifestations
Distal muscle atrophy causing pes cavus and stork leg deformity; distal sensory loss.
Diagnosis
Nerve conduction studies show markedly slowed conduction velocities; genetic testing confirms.
Treatment
No curative therapy; physical therapy and orthotics are the mainstays of management.
Prognosis
Slowly progressive; normal life expectancy with rare respiratory involvement.
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Epidemiology & Etiology
This is the most common inherited peripheral neuropathy, often presenting in the first or second decade of life. It is primarily autosomal dominant, though X-linked and recessive forms exist. It is characterized by a progressive loss of muscle tissue and touch sensation across various parts of the body.
Pertinent Anatomy
The disease primarily affects the peripheral nerves and the distal muscles of the lower extremities. The peroneal nerve is typically the first to be affected, leading to the classic gait disturbances.
Pathophysiology
The condition involves mutations in genes responsible for myelin production or axonal maintenance. This leads to chronic demyelination or axonal degeneration of peripheral nerves. The resulting distal nerve damage causes secondary muscle atrophy due to chronic denervation.
Clinical Manifestations
Patients present with distal muscle weakness and atrophy, classically described as stork leg deformity or inverted champagne bottle legs. Physical exam reveals pes cavus (high arches) and hammer toes. Red flags include severe respiratory muscle weakness, which is rare but indicates a poor prognosis.
Diagnosis
Nerve conduction studies are the gold standard, demonstrating markedly slowed conduction velocities (typically <38 m/s). Genetic testing is the definitive diagnostic tool to identify specific mutations. Electromyography (EMG) may show signs of chronic denervation.
Treatment
Management is supportive, focusing on physical therapy and occupational therapy to maintain mobility. Ankle-foot orthotics (AFO) are frequently used to correct foot drop. Avoid neurotoxic drugs such as vincristine, which can exacerbate neuropathy.
Prognosis
The disease is slowly progressive but generally does not affect life expectancy. Patients require regular monitoring for orthopedic deformities and gait instability. Most patients remain ambulatory throughout their lives.
Differential Diagnosis
Friedreich Ataxia: presence of ataxia and hypertrophic cardiomyopathy
Chronic Inflammatory Demyelinating Polyneuropathy: rapid onset and elevated CSF protein
Diabetic Neuropathy: associated with hyperglycemia and metabolic history
Amyotrophic Lateral Sclerosis: presence of upper motor neuron signs
Distal Myopathy: lack of sensory involvement