Orthopaedic Surgery - Charcot–Marie–Tooth Disease (Hereditary Sensorimotor Neuropathy)

Basics

Charcot–Marie–Tooth disease (CMT) is the most common inherited motor and sensory peripheral neuropathy.

It represents the final common clinical manifestation of numerous genetic abnormalities, involving more than 80 recognized genes, that impair normal peripheral nerve signaling.

The disorder typically progresses in a distal-to-proximal pattern. Distal lower-extremity muscle wasting and weakness develop first, often resulting in cavovarus foot deformity. In some patients, weakness later involves the upper extremities.

Classification

Several major clinical and genetic forms of CMT are recognized.

The five commonly described groups are Type I, Type II, Type III, Type IV, and X-linked CMT.

Type I CMT

Type I is the hypertrophic demyelinating form and accounts for approximately half of affected patients.

The peripheral nerves become thickened because of abnormal myelin formation and repeated demyelination.

Loss of normal myelin causes marked slowing of peripheral nerve conduction.

Type II CMT

Type II is predominantly an axonal form of the disease.

Axonal degeneration produces weakness and sensory abnormalities, while the myelin sheath is relatively preserved.

Nerve conduction velocities are therefore usually only mildly reduced compared with the marked slowing seen in demyelinating disease.

Reflexes may remain relatively preserved.

Type III CMT

Type III, traditionally called Dejerine–Sottas disease, is characterized by marked segmental demyelination.

It is generally a more severe neuropathy and may present earlier than the common forms of CMT.

Type IV CMT

Type IV consists of forms inherited in an autosomal recessive pattern.

The severity and clinical manifestations vary according to the specific genetic abnormality.

X-Linked CMT

CMT-X is inherited through the X chromosome and accounts for approximately 10% of cases.

The severity of disease may differ according to the specific mutation and sex of the affected patient.

Genetics

CMT is genetically heterogeneous.

A particularly important abnormality in common demyelinating forms involves the gene encoding peripheral myelin protein 22-kDa (PMP22).

Other CMT subtypes result from mutations affecting peripheral nerve myelin, axonal structure, intracellular transport, or other components of nerve function.

Inheritance Patterns

Autosomal dominant inheritance with variable penetrance occurs in many forms of Types I, II, and III.

Type IV follows an autosomal recessive pattern.

CMT-X is inherited through the X chromosome.

A detailed family history is therefore an important part of the diagnostic evaluation.

Pathophysiology

Muscle weakness generally progresses from the distal extremities proximally.

In the lower leg, the tibialis anterior and peroneus brevis are commonly affected early.

Selective weakness of these muscles produces characteristic imbalance around the foot and ankle and contributes to development of cavovarus deformity.

Development of Cavus

Weakness of the tibialis anterior allows the peroneus longus to act relatively unopposed.

The peroneus longus plantarflexes the first ray, producing a plantarflexed first metatarsal and contributing to elevation of the medial longitudinal arch.

Development of Hindfoot Varus

Weakness of the peroneus brevis allows the posterior tibialis to dominate.

The resulting inversion force drives the hindfoot into varus.

Toe Clawing

Weakness of the intrinsic muscles and lumbricals allows the long flexor and extensor tendons to overpower the intrinsic musculature.

This imbalance leads to the characteristic clawing of the toes.

Dynamic Hindfoot Inversion

Plantarflexion of the first metatarsal can dynamically force the hindfoot into inversion during weight-bearing.

This mechanism is responsible for a forefoot-driven cavovarus deformity in many patients.

Progressive Rigidity

As the deformity persists, soft-tissue contracture and bony remodeling progressively reduce foot flexibility.

The foot becomes increasingly rigid, with impaired shock absorption and abnormal loading through the hindfoot and midfoot.

Arthritis

Longstanding malalignment and abnormal joint loading may eventually produce degenerative arthritis.

The subtalar, midfoot, and ankle joints may become painful and stiff.

Ankle Instability

Persistent hindfoot varus repeatedly stresses the lateral ankle ligaments.

Over time, ligament attenuation may lead to recurrent ankle sprains and chronic lateral ankle instability.

Associated Conditions

CMT may be associated with musculoskeletal abnormalities outside the foot.

Important associated conditions include scoliosis and developmental dysplasia of the hip.

Scoliosis

Approximately 30% of patients may develop scoliosis.

A proportion of these patients have left thoracic curves, and significant thoracic kyphosis may also be present.

Hip Dysplasia

Developmental dysplasia of the hip occurs in approximately 6–8% of patients.

Hip motion, particularly abduction, should therefore be examined routinely.

Diagnosis

Signs and Symptoms

Patients commonly become symptomatic between approximately 10 and 20 years of age.

Typical presentations include a high medial arch, reduced endurance, decreased coordination, recurrent ankle instability, or a characteristic steppage gait.

Footwear Problems

Progressive cavovarus alignment produces uneven plantar loading.

Shoes may wear out rapidly and asymmetrically, especially along the lateral border.

Muscle Weakness Pattern

Weakness generally appears first in the ankle evertors and dorsiflexors.

The plantarflexors and invertors are typically affected later.

This imbalance contributes substantially to cavus and hindfoot varus.

Sensory Changes

Sensation and proprioception may be diminished.

Reduced proprioceptive input can worsen balance, gait control, and ankle instability.

Steppage Gait

Foot-drop weakness can produce a steppage gait.

The patient excessively flexes the hip and knee during the swing phase so that the toes clear the floor.

Circumduction Gait

Some patients compensate by swinging the affected limb outward in a circumduction pattern during the swing phase.

History

A detailed family history should identify relatives with high arches, claw toes, similar gait abnormalities, distal weakness, or a known diagnosis of CMT.

The rate of progression of weakness and deformity should also be documented.

Ankle Instability History

Patients should be questioned about repeated ankle sprains, giving-way episodes, or feelings of instability.

These symptoms may indicate chronic lateral ligament insufficiency caused by cavovarus alignment.

Pain History

Pain should be localized carefully.

Common symptomatic areas include the lateral ankle, plantar forefoot, midfoot, and sites of callus formation.

Physical Examination

The examination should assess muscle bulk, strength, sensation, foot alignment, deformity flexibility, gait, hip motion, spinal alignment, and upper-extremity involvement.

Calf Atrophy

Distal lower-extremity muscle wasting commonly produces visible calf atrophy.

Muscle Strength

The strength of all major foot and ankle muscle groups should be recorded and followed over time.

Particular attention should be given to dorsiflexion, eversion, inversion, and plantarflexion.

Sensory Examination

Sensation should be assessed, including light touch, proprioception, and protective sensation.

Reduced protective sensation increases the risk of pressure injury from abnormal foot loading.

Hindfoot Varus

The patient should be examined standing and at rest for the presence of hindfoot varus.

The severity of hindfoot varus is closely related to functional impairment, ankle instability, and lateral overload.

Coleman Block Test

The Coleman block test helps distinguish flexible from fixed hindfoot varus.

The patient stands with the heel and lateral border of the foot supported while the first ray hangs freely beyond the edge of the block.

If the heel corrects toward neutral, the hindfoot remains flexible and the varus is largely driven by the plantarflexed first ray.

Passive Hindfoot Correction

Manual correction of hindfoot varus should also be assessed.

A rigid deformity is more likely to require bony correction rather than soft-tissue procedures alone.

Lateral Ankle Ligaments

The lateral ankle ligaments should be examined for laxity and mechanical instability.

Chronic varus positioning can progressively stretch these structures.

First Metatarsal Position

The relative position of the first metatarsal should be compared with the lesser metatarsals.

A plantarflexed first ray is characteristic of CMT-associated cavus.

Toe Clawing

The presence and severity of clawing should be documented.

The examiner should determine whether the toe deformities are flexible or fixed.

Gait Examination

Gait should be observed for foot drop, steppage, circumduction, ankle instability, and abnormal push-off.

Functional gait findings help determine the clinical severity of disease.

Hip Examination

Hip abduction should be measured.

Restricted abduction may suggest associated hip dysplasia and should prompt further imaging.

Spine Examination

The spine should be evaluated for scoliosis using a forward-bend test and observation of shoulder and trunk symmetry.

Upper-Extremity Examination

The hands should be inspected for wasting of the ulnar-innervated intrinsic muscles, including the interossei and abductors.

Upper-extremity weakness tends to develop later than lower-extremity involvement.

Electrodiagnostic Studies

Electromyography and nerve conduction studies are commonly used to confirm the diagnosis and characterize the neuropathy.

They help distinguish predominantly demyelinating disease from axonal forms.

Electromyography

EMG may demonstrate increased motor unit duration and reduced amplitude, reflecting chronic denervation and reinnervation.

Nerve Conduction Studies

Motor and sensory nerve conduction velocities are reduced to varying degrees.

Marked slowing is especially characteristic of demyelinating forms such as CMT Type I.

Hand Function Testing

Grip strength and manual dexterity may be monitored over time.

The 9-hole peg test can be used to quantify changes in fine motor function.

Biopsy

Muscle and nerve biopsy are rarely required when the history, examination, electrodiagnostic findings, and genetic testing are characteristic.

Muscle Biopsy Findings

Muscle biopsy may demonstrate diffuse atrophy with replacement of normal muscle fibers by fibrous and adipose tissue.

Nerve Biopsy Findings

Nerve biopsy may show loss of myelinated fibers and increased fibrous tissue within the endoneurium and perineurium.

Because genetic and electrodiagnostic testing are less invasive, biopsy is generally unnecessary.

Genetic Testing

DNA testing can be performed from peripheral blood.

It may confirm the diagnosis, identify a specific subtype, allow testing of family members, and assist with genetic counseling.

Imaging

Standing Foot and Ankle Radiographs

Weight-bearing radiographs should be obtained to evaluate cavus alignment, hindfoot varus, first-ray plantarflexion, joint congruity, and degenerative arthritis.

They are particularly important for surgical planning.

Spine Radiographs

In an index patient without a known family history, spinal radiographs may be obtained to exclude other structural causes of cavus deformity.

They are also appropriate when scoliosis is identified clinically.

Pelvic Radiographs

Pelvic radiographs should be considered when hip abduction is limited or dysplasia is suspected.

Early identification of hip dysplasia allows more effective treatment.

MRI of the Spine

Spinal MRI may be appropriate when the diagnosis is uncertain or there is concern for spinal pathology.

It can demonstrate abnormalities of the spinal cord and help exclude other neurologic causes of cavus deformity.

Differential Diagnosis

Important differential diagnoses include tethered spinal cord, myelomeningocele, lipomeningocele, peroneal nerve palsy, early Duchenne muscular dystrophy, and other hereditary motor and sensory neuropathies.

An atypical or unilateral deformity should prompt particularly careful investigation for a focal neurologic cause.

Treatment

General Principles

Treatment aims to maintain mobility, preserve flexibility, improve alignment, reduce pain, support weak muscles, and prevent progression of secondary deformity.

Orthopaedic treatment cannot reverse the underlying genetic neuropathy.

Routine Surveillance

Patients should be followed regularly for progression of muscle weakness, foot deformity, ankle instability, sensory loss, and functional limitation.

Earlier treatment may prevent a flexible deformity from becoming rigid.

Stretching

Regular stretching of the Achilles tendon and plantar fascia may help preserve foot and ankle flexibility.

Stretching is most useful before fixed contracture has developed.

Orthotic Insoles

Custom orthoses can redistribute plantar pressure and improve alignment.

A lateral heel build-up or wedge may help reduce flexible hindfoot varus.

Forefoot Padding

Accommodative padding beneath the forefoot may help relieve metatarsalgia and pressure associated with claw toes.

Ankle Bracing

An ankle brace may provide support in patients with symptomatic instability or recurrent ankle sprains.

Ankle-Foot Orthosis

A custom ankle-foot orthosis (AFO) may be necessary for substantial foot drop caused by dorsiflexor weakness.

It improves toe clearance during swing and may reduce falls.

Footwear

Comfortable footwear with a wide toe box, adequate depth, and cushioned heel is recommended.

Shoes should accommodate claw toes, high arches, and pressure-sensitive areas.

Physical Therapy

Physical therapy may include Achilles and plantar fascia stretching, strengthening exercises, gait work, proprioceptive training, and balance exercises.

These measures can improve function and reduce instability but do not reverse the neuropathy itself.

Surgery

General Surgical Principles

Surgical treatment should be individualized according to the flexibility and location of the deformity.

As a general principle, flexible deformities are managed with soft-tissue releases, rigid deformities require osteotomies, and tendon transfers are used to rebalance abnormal muscle forces.

The goal is to obtain a stable, plantigrade, pain-free, and braceable foot.

Claw-Toe Correction

Claw toes may be treated with flexor-to-extensor tendon transfer, MTP joint release, or PIP joint fusion, depending on whether the deformity remains flexible.

Jones Procedure

Severe hallux clawing may be treated with hallux interphalangeal arthrodesis combined with transfer of the extensor hallucis longus tendon to the first metatarsal.

This combination is commonly known as a Jones procedure.

Plantar Release

Soft-tissue release may involve the plantar fascia, abductor hallucis, and toe flexors.

This helps reduce the cavus deformity and increase flexibility.

Plantar-Medial Release

More extensive deformity may require a plantar-medial release involving structures such as the posterior tibialis, long toe flexors, and talonavicular capsule.

Posterior Tibialis Transfer

The posterior tibialis tendon may be transferred partially or completely toward the anterior aspect of the foot.

This can improve dorsiflexion and eversion while reducing the deforming inversion force.

Peroneus Longus to Brevis Transfer

Transfer or tenodesis of the peroneus longus to the peroneus brevis reduces plantarflexion of the first ray and increases eversion strength.

This is particularly useful in flexible forefoot-driven cavovarus deformity.

Calcaneal Osteotomy

A lateral closing-wedge calcaneal osteotomy may be required when hindfoot varus is rigid.

The procedure repositions the heel toward neutral alignment.

Midfoot and Metatarsal Osteotomies

Rigid cavus involving the forefoot or midfoot may require midfoot or metatarsal closing-wedge osteotomies.

These procedures reduce the high arch and improve plantar pressure distribution.

Triple Arthrodesis

Triple arthrodesis is generally reserved for severe rigid deformity or painful hindfoot arthritis.

Fusion sacrifices motion but can provide a stable and better-aligned foot.

Ankle Ligament Reconstruction

Chronic lateral ankle instability may require ligament reconstruction.

The underlying cavovarus deformity should also be corrected because isolated ligament repair may fail if varus alignment persists.

Follow-Up

Specialist Referral

Neurologic consultation is appropriate for electrodiagnostic evaluation, genetic testing, and counseling.

Management often benefits from collaboration among neurology, orthopaedics, physical therapy, orthotics, and genetics specialists.

Prognosis

Even after appropriate surgery, the foot generally cannot be restored completely to normal because the underlying muscle weakness continues.

Progressive neuropathy may lead to further weakness or recurrence of deformity.

Life Expectancy

Typical Charcot–Marie–Tooth disease does not shorten life expectancy.

Most morbidity relates to progressive weakness, deformity, gait difficulty, and loss of distal function.

Recurrence

Deformity can recur after surgery, especially when soft-tissue procedures alone are used in a foot that already has fixed bony malalignment.

Successful reconstruction requires correction of both structural deformity and muscle imbalance.

Adjacent-Joint Degeneration

Fusion procedures, particularly triple arthrodesis, may transfer mechanical stress to neighboring joints.

This can contribute to later degeneration of the ankle or midfoot.

Hip Dysplasia

Failure to recognize associated hip dysplasia may make later treatment more difficult and less successful.

Routine hip examination is therefore important throughout growth.

Patient Monitoring

Patients should generally be reviewed yearly for ambulatory function, muscle strength, foot alignment, ankle stability, sensory changes, hand function, and spinal deformity.

Earlier reassessment is appropriate if there is rapid deterioration, new weakness, recurrent falls, worsening pain, or progression of deformity.