Charcot Marie Tooth Disease (Hereditary Motor and Sensory Neuropathy)

Key Points:

  • Charcot Marie Tooth (CMT) disease is also referred to as Hereditary motor and sensory neuropathy (HMSN)
  • Occurs as a result of a duplication on chromosome 17 affecting peripheral myelin protein 22
  • Frequently presents with cavus foot deformity with claw toes and gait abnormalities (steppage gait and/or foot drop)
  • Later in the disease process, progressive weakness of the hands, tongue and feet is noted
  • Associated orthopaedic conditions: hip dysplasia and scoliosis

Description:

Charcot-Marie-Tooth disease, hereditary motor and sensory neuropathy (HMSN), is one of the most common inherited neurologic disorders.   It affects the peripheral nervous system and was originally named for the first three physicians to identify the disorder.

Epidemiology:

CMT disorder has an incidence between 1/2500 to 1/5000 people in the United States.

Clinical Findings:

The onset is gradual with variable timing of initial presentation, most common in the second decade of life.  Progressive weakness, distal muscle atrophy, and diminished tendon reflexes are characteristic findings. Sensory loss is common, yet often not recognized by the patient. A history of worsening gait (walking and/or running) and frequent ankle sprains is common.  

Foot deformity is often the first musculoskeletal manifestation.  This is related to muscle imbalance, with the peroneus longus overpowering a weakened tibialis anterior, resulting in a plantarflexed first ray and a cavus foot. The hindfoot will adopts a varus posture, which may be flexible or rigid.  The Coleman block test is used to assess the flexibility of the hindfoot.  Cavovarus foot deformity is frequently symptomatic due to the presence plantar callosities or ankle instability. Claw toe deformities frequently coexist and may be symptomatic due to pressure within the shoe.

Weakness in the lower extremities may yield a steppage gait and/or a foot drop.  With disease progression, weakness develops in the hand intrinsics, impairing fine motor skills and in the tongue, producing difficulty swallowing.
Patients with CMT have an increased risk of scoliosis, which may occur in up to 37% of patients.  The curves are often atypical such as a left thoracic or with excessive kyphosis.  The presence of hip dysplasia should be aggressively sought, as it may be asymptomatic initially.

Imaging Studies:

Referral to a pediatric neurologist for further testing is appropriate when there is a suspicion of CMT.  A blood test can identify 80-90% of known gene mutations.  Electromyography and nerve conduction studies may be considered if genetic testing is inconclusive.  Reduced nerve conduction velocities are identified in the demyelinating forms of CMT.  

For musculoskeletal manifestations of CMT, the orthopaedic surgeon should consider image according to the clinical findings and symptoms.  Foot, spine, hip and pelvis radiographs are often appropriate. 

Etiology:

HMSN is caused by a gene mutation affecting the structure and function of the peripheral nerve axon or the myelin sheath.  It is most commonly autosomal dominant and occurs as a result of a duplication on chromosome 17.  This region codes for peripheral myelin protein 22 (PMP 22).

Classification

CMT 1, 2, and 3 are the most common.  The following is a breakdown of the type and the commonly affected portion of the nerve: 

  • CMT 1 – Abnormalities in myelin sheath, three subtypes (A, B, C).
  • CMT 2 – Abnormalities in axon, 1/3 less common than CMT1.
  • CMT 3 – Dejerine-Sottas disease, a severe demyelinating disease that starts in infancy. Point mutation on PMP-22 gene.
  • CMT4 – Several subtypes each with different gene mutation.
  • CMT X – Abnormal gap junction communication, X-linked dominant.

Treatment:

As with any disease which affects a variety of musculoskeletal areas, the orthopaedic surgeon treats according to the area of concern.

For most foot problems where the deformity remains flexible, the first line of treatment is physical therapy, followed by orthotics (lateral posting of the forefoot & heel). A supramalleolar orthosis (SMO) or ankle foot orthosis (AFO) may improve balance and help with recurrent ankle instability. With progressive deformity and symptoms, surgery is indicated.  In the young child, soft-tissue releases and/or tendon transfers improve the position of the foot and permit comfortable use of an orthotic. For older patients with more severe deformity, the surgery needs to address all the components of the deformity.  The first ray is addressed with a dorsiflexing osteotomy, the plantar fascia is released, and tendon transfers are performed to balance the muscles (typically peroneous longus to brevis and/or tibialis posterior to the anterior midfoot). If there is an abnormal Coleman block test preoperatively, a valgus calcaneal osteotomy should be considered.  If the deformity is rigid, a triple arthrodesis may be required.  Claw toes can be treated with a Jones procedure (transfer of long extensor tendons into metatarsal neck).

Pelvic osteotomies may be recommended based on the presence of hip dysplasia.  For patients with scoliosis, bracing is rarely effective but is appropriate to consider.  Posterior spinal fusion is typically recommended with indications similar to idiopathic scoliosis.

Complications:

Late diagnosis of scoliosis or hip dysplasia.

References:

  1. Alexander IJ, Johnson KA. Assessment and management of pes cavus in Charcot-Marie-Tooth disease. Clin Orthop Relat Res. 1989 Sep; (246): 273-81.
  2. Mann RA, Missirian J. Pathophysiology of Charcot-Marie-Tooth disease. Clin Orthop Relat Res . 1988 Sep; (234): 221-8.
  3. Roper BA, Tibrewal SB. Soft tissue surgery in Charcot-Marie-Tooth disease. J Bone Joint Surg Br. 1989 Jan; 71 (1): 17-20.
  4. Ward CM, Dolan LA, Bennett DL, Morcuende JA, Cooper RR. Long-term results of reconstruction for treatment of a flexible cavocarus foot in Charcot-Marie-Tooth Disease. J Bone Joint Surg. 2008 Dec; 90 (12): 2631-42.
  5. Wetmore RS, Drennan JC. Long-term results of triple arthrodesis in Charcot-Marie-Tooth disease. J Bone Joint Surg. 1989 Mar; 71 (3): 417-22.
  6. Wilmshurst JM, Ouvrier R. Hereditary peripheral neuropathies of childhood: an overview for clinicians. Neuromuscular disorders. 2011 Nov; 21 (11): 763-75.

Top Contributors:

Dana Olszewski, MD, MPH