Stat Consult: Charcot-Marie-Tooth Disease- Clinical Advisor


  • Peroneal muscular dystrophy (CMT) disease is a group of inherited sensory and motor neuropathies caused by demyelination, axonal dysfunction, or both
  • Most common inherited neuropathy and most common neuromuscular disease in children; reported prevalence 1:3,300
  • 70%-80% of cases are caused by somatic dominant inheritance (the most common), somatic recessive or X-linked mutations, or de novo mutations in the disease-causing gene
  • Symptoms usually begin in the first to third decades of life and progress slowly
  • There are 5 main types of CMT diseases based on inheritance patterns and molecular genetics
    • Peroneal muscular dystrophy type 1 (CMT1), CMT2, CMT3 (or intermediate), CMT4, and CMTX
  • Complications of CMT disease may include breathing and sleep disorders, mobility problems, and weakness in the limbs.
  • There is no effective treatment for CMT, The focus is on optimizing quality of life
    • The impact of symptoms is greatest in the first decade after diagnosis
    • Symptoms that affect quality of life include:
      • Difficulty driving distance
      • Weakness in upper and lower limbs
      • Respiratory and sleep disorders


  • The peripheral nervous system maintains the integrity of its anatomical structures to propagate electrical impulses between motor neurons and muscles, sensory receptors and sensory neurons
  • CMT diseases affect the peripheral nervous system through certain genetic mutations, leading to one or both of demyelination and axonal pathology.
    • Demyelination (the most common form of CMT) is caused by:
      • Defects in myelinating Schwann cells
      • Peripheral myelination disorders PMP22, MPZ, Guojie B1and Exhaust gas recirculation 2
      • overexpression PMP22 In CMT1A, results in toxic protein aggregation and protein degradation processes
      • disease-causing genetic variant MPZ CMT1B, causing major peripheral myelin protein abnormalities
    • Axonal pathology (a less common form of CMT) results from:
      • Major abnormalities in nerve axons and/or their interactions with Schwann cells, affecting motor and sensory/autonomic nerves
      • Axonal structural maintenance and aberrations in axonal function Most Favored Nation 2, Gross Domestic Product1, RAB7, TRP4and guys

Clinical manifestations and physical examination findings

  • Symptoms usually begin between the first and third decades of life and progress slowly; common symptoms and physical findings include:
    • foot deformity
      • High cavus (common)
      • Thinning of the ankle (recommended for more advanced cases)
      • Atrophy of the anterior and/or posterior compartment of the calf (suggesting more advanced cases)
    • Hand involvement, such as mild atrophy (flattening) of the hypothenar muscle and the base of the thenar muscle
    • Loss of sensation and weakness in limbs; assess losses:
  • In children, the earliest characteristics are often nonspecific but may include:
    • Walking on tiptoes with stumbling/falling
    • Weakness in the hands (causing difficulty in dressing, tying shoes, or writing)
    • Retarded motor development
    • Numbness, tingling, or pain, although children may not complain of these symptoms
    • Flat feet or high arches (asymmetric foot alignment is not typical)
    • Muscle spasms (possibly suggestive of axonal form of CMT)
  • Dejerine-Sottas syndrome — A rare infantile form of severely demyelinating CMT that presents with nonspecific clinical signs such as:
    • Breathing problems (when severe)

Medical history and family history

  • Ask about
    • Foot deformities/gait problems
    • Muscle spasm (usually gastrocnemius, associated with reduced ankle range of motion/toe walking)
  • Ask about family history of CMT disease or other neuropathies

make a diagnosis

  • A suspect diagnosis in patients with distal muscle weakness and atrophy, mild to moderate sensory loss, diminished tendon reflexes, pes cavus, and more than one of the following:
    • family history of neuropathy
    • Other foot abnormalities, such as hammertoes or clubfoot
    • Gait disorders, especially flail, pes cavus, or toe walking
  • Diagnosis should be confirmed by:
    • Electromyography (EMG)
      • Almost all patients with CMT disease have abnormal electromyography
      • May help differentiate between acquired and inherited neuropathies and rule out other types of neuromuscular disorders
      • The test is minimally invasive and can be used on patients of any age
      • Surface electrodes can be used to assess motor and sensory nerves
      • Needle examination can provide evidence of acute/chronic denervation patterns, which can help determine whether the neuropathy is axonal or demyelinating
    • Nerve conduction velocity (NCV)
      • Almost all patients with CMT disease have abnormal NCV
      • Motor nerve fiber conduction velocity can differentiate between demyelinating CMT and axonal CMT
      • Demyelination is demonstrated when motor nerve conduction slows
        • Upper limb < 30 m/s
        • Lower limbs < 25 m/s
      • Uniform nerve conduction slowing is characteristic of peroneal muscular atrophy type 1A (CMT1A); CMTX is characterized by variable conduction velocities
  • Consider molecular genetic testing to confirm the diagnosis if:
    • Electromyography and nerve conduction velocity measurements are equivalent
    • There is a known familial mutation
    • Consider testing first the single-gene pathogenic variant that best fits the clinical presentation
    • mutation in PMP22, Guojie B1, MPZand Most Favored Nation 2 Very common in CMT and should be sequenced before further genetic testing
  • Sural nerve biopsy is not routinely performed but is sometimes helpful in diagnosing CMT hereditary neuropathy because characteristic lesions can be found compared with other neuropathies.

Management overview

  • There is no effective treatment for CMT
  • Physical therapy and braces are the backbone of supportive care
    • Refer the patient for regular physical therapy focusing on strength, range of motion, and balance training to maintain the patient's mobility
    • Patients are advised to perform daily:
      • Heel cord stretches prevent Achilles tendon shortening
      • Grip exercises for weak hands
    • Consider the patient's gait, pain, strength and stability when selecting an orthotic
    • Refer patients for gait training and occupational therapy as needed
  • drug
    • Consider short-term medication to treat CMT-related symptoms, but long-term use of some medications may be problematic
    • For musculoskeletal pain, give acetaminophen or nonsteroidal anti-inflammatory (NSAID) drugs
    • For neuropathic pain, consider tricyclic antidepressants or medications such as carbamazepine or gabapentin
    • For fatigue, consider modafinil
  • Operation
    • Consider orthopedic surgery to correct:
      • Severe sunken deformity of foot
    • For patients with chronic ankle injuries or pain that orthotics do not relieve, consider surgical correction


  • Complications that may occur in people with CMT include:
    • Daytime sleepiness/poor sleep quality
    • Esophageal dysphagia or oropharyngeal dysphagia
    • Pregnancy complications and sexual dysfunction
    • restrictive lung injury

Kendra Church MS, PA-C, is a physician assistant at Dana-Farber Cancer Institute/Brigham and Women's Hospital and a senior clinical editor at DynaMed, an evidence-based point-of-care database.


1. Yiu EM, Bray P, Baets J, et al. Clinical practice guidelines for the treatment of pediatric peroneal muscular atrophy. Journal of Neurosurgical Psychiatry. 2022;93(5):530-538. doi:10.1136/jnnp-2021-328483

2. Introduction to Bird TD, hereditary neuropathy of peroneal muscles. See: Adam MP, Mirzaa GM, Pagon RA, etc. edit. genetic review [Internet]. University of Washington, Seattle; September 28, 1998.

3. Jani-Acsadi A, Ounpuu S, Piertz K, Ascadi G. North American Pediatric Clinics. 2015;62(3):767-786. doi:10.1016/j.pcl.2015.03.012

4. McCorquodale D, Pucillo EM, Johnson NE. Management of peroneal muscular atrophy: improving long-term care through a multidisciplinary approach. Journal of Multidisciplinary Health. 2016;9:7-19. Number: 10.2147/JMDH.S69979

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