Hereditary Neuropathies: Charcot-Marie-Tooth Disease

CHAPTER 64

Hereditary Neuropathies: Charcot-Marie-Tooth Disease

Introduction/Etiology/Epidemiology

• Charcot-Marie-Tooth (CMT) disease is a common form of polyneuropathy considered a hereditary sensory and motor neuropathy.

• It manifests with symmetric weakness of distal muscles, especially of the lower extremities.

• Hallmark presentation is the cavus foot due to selective functional loss of the anterior compartment muscles of the lower extremities

• Prevalence is 1 in 2,500 individuals

• The most common form of inheritance is autosomal dominant, but other subtypes can be autosomal recessive or X-linked.

• The 2 main subtypes are CMT 1 and CMT 2.

— CMT 1 (hypertrophic or demyelinating type) is most common, accounting for 60% to 80% of cases.

— CMT 2 (axonal or neuronal type) accounts for 20% to 40% of cases. The disease progresses very slowly, with a highly variable severity.

• Clinical findings in CMT are caused by disrupted axonal transport and impaired intracellular protein trafficking.

• Since the mid-1990s, more than 30 affected genes have been identified in cases of CMT, and many more may ultimately be described.

Signs and Symptoms

• Onset of CMT 1 typically occurs in adolescence or early adulthood.

• Onset of CMT 2 is at an older age, often in the third decade after birth.

• Early symptoms include frequent tripping, toe walking, foot pain caused by cavovarus foot deformity, and unstable ankles.

• Foot problems such as cavovarus foot are the most common orthopaedic manifestation of CMT.

— Atrophy and contracture of the intrinsic muscles of the foot, contracture of the plantar fascia, and weakness of the peroneus brevis and anterior tibialis lead to foot changes, including plantar flexion of the first ray, forefoot equinus, and hindfoot varus (Figure 64-1).

— The probability of a patient with bilateral cavovarus feet being diagnosed with CMT, regardless of family history, is as high as 78%.

• Weakness of the upper limbs presents later in the disease and slowly progresses proximally, ultimately affecting the hands, forearms, and upper arms.

• Physical examination findings

— Cavovarus (high arch) foot deformity

— Tight heel cords

— Inability to walk on heels

— Calf muscle atrophy causes a stork leg.

— Claw toes or hammer toes

— Plantar flexed first metatarsal

— Intrinsic muscle atrophy of the hand and feet occurs as early as the first decade or as late as the third decade (Figure 64-2).

■Difficulty with thumb opposition and side-to-side pinch

■Clawing of the fingers, with ring and small digits affected first

■In general, muscles innervated by ulnar and peroneal nerves are affected, while those innervated by the radial and tibial nerves are spared.

— Diminished or absent deep tendon reflexes (DTRs), especially at the ankles

■Knee reflexes are affected after ankle reflexes.

■DTRs are usually normal in CMT 2.

Figure 64-1. Cavus foot in a child with Charcot-Marie-Tooth disease.

From Armstrong AD, Hubbard MC, eds. Essentials of Musculoskeletal Care. 5th ed. Rosemont, IL: American Academy of Orthopaedic Surgeons; 2016:1047. Reproduced with permission.