Skip to main content

Advertisement

SpringerLink
Log in

Charcot-Marie-Tooth disease

  • Published:
Current Treatment Options in Neurology Aims and scope Submit manuscript

Opinion statement

The family of hereditary peripheral neuropathies that makes up Charcot-Marie-Tooth disease (CMT) comprises some of the most common neuromuscular disorders. Over the past decade, understanding of the molecular basis of CMT has increased enormously. In addition, the neurophysiologic deficits and clinical problems associated with CMT are more clearly delineated, and the precise genetic cause of many types of CMT has now been determined. Advances in molecular biology and genetic manipulation techniques have allowed the development of animal models of some of these CMT types, allowing more productive scientific exploration of possible treatments. Recent treatment advances that have been effective in animal models include oral supplementation with curcumin and vitamin C (ascorbic acid), and the use of onapristone, a progesterone antagonist. Human trials with vitamin C are currently in progress. While ongoing molecular genetic research continues to identify more of the mutant genes and proteins that cause the various disease subtypes, clinical research should continue to focus on developing pharmaceutical and rehabilitative therapies to ameliorate nerve degeneration and ultimately improve function for patients with CMT. These patients optimally should be managed in a comprehensive, multidisciplinary setting involving neurologists, physiatrists, orthopedic surgeons, physical and occupational therapists, and orthotists. Treatment should be aimed at maximizing independence and quality of life.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Carter GT, Abresch RT, Fowler WM, et al.: Profiles of neuromuscular disease: hereditary motor and sensory neuropathy, types I and II. Am J Phys Med Rehabil 1995, 74:S140–S149.

    Article  PubMed  CAS  Google Scholar 

  2. Street V, Meekins G, Lipe HP, et al.: Charcot-Marie-Tooth neuropathy: phenotypes and genotypes of four new mutations in the MPZ and Cx 32 genes. Neuromusc Disord 2002, 12:643–650.

    Article  PubMed  CAS  Google Scholar 

  3. Abresch RT, Jensen MP, Carter GT: Health quality of life in peripheral neuropathy. Phys Med Rehabil Clin N Am 2001, 12:461–472.

    PubMed  CAS  Google Scholar 

  4. Lindeman E, Leffers P, Reulen J, et al.: Quadriceps strength and timed motor performances in myotonic dystrophy, Charcot-Marie-Tooth disease, and healthy subjects. Clin Rehabil 1998, 12:127–135.

    Article  PubMed  CAS  Google Scholar 

  5. Lindeman E, Leffers P, Spaans F, et al.: Strength training in patients with myotonic dystrophy and hereditary motor and sensory neuropathy: a randomized clinical trial. Arch Phys Med Rehabil 1995, 76:612–620.

    Article  PubMed  CAS  Google Scholar 

  6. Lindeman E, Leffers P, Spaans F, et al.: Deterioration of motor function in myotonic dystrophy and hereditary motor and sensory neuropathy. Scand J Rehabil Med 1995, 27:59–64.

    PubMed  CAS  Google Scholar 

  7. Lindeman E, Leffers P, Reulen J, et al.: Reduction of knee torques and leg-related functional abilities in hereditary motor and sensory neuropathy. Arch Phys Med Rehabil 1994, 75:1201–1205.

    Article  PubMed  CAS  Google Scholar 

  8. Carter GT, Kilmer DD, Szabo RM, McDonald CM: Focal posterior interosseus neuropathy in the presence of hereditary motor and sensory neuropathy, type I. Muscle Nerve 1996, 19:644–648.

    Article  PubMed  CAS  Google Scholar 

  9. Bienfait HM, Baas F, Koelman JH, et al.: Phenotype of Charcot-Marie-Tooth disease type 2. Neurology 2007, 68:1658–1667.

    Article  PubMed  CAS  Google Scholar 

  10. Carter GT, England JD, Hecht TW, et al.: Electrodiagnosis of hereditary motor and sensory neuropathies. Phys Med Rehabil Clin N Am 2003, 14:347–363.

    PubMed  Google Scholar 

  11. Meekins GD, Carter GT, Emery MJ, Weiss MD: Axonal degeneration in the Trembler-j mouse evident by stimulated single-fiber electromyography. Muscle Nerve 2007, 36:81–86.

    Article  PubMed  CAS  Google Scholar 

  12. Carter GT, Kilmer DD, Bonekat HW, et al.: Evaluation of phrenic nerve and pulmonary function in hereditary motor and sensory neuropathy, type I. Muscle Nerve 1992, 15:459–462.

    Article  PubMed  CAS  Google Scholar 

  13. Meekins GD, Weiss MD: Electrodiagnostic studies in a murine model of demyelinating Charcot-Marie-Tooth disease. Phys Med Rehabil Clin N Am 2005, 16:967–979.

    PubMed  Google Scholar 

  14. Carter GT, Jensen MP, Galer BS, et al.: Neuropathic pain in Charcot-Marie-Tooth disease. Arch Phys Med Rehabil 1998, 79:1560–1564.

    Article  PubMed  CAS  Google Scholar 

  15. Chetlin RD, Gutmann L, Tarnopolsky MA, et al.: Resistance training effectiveness in patients with Charcot-Marie-Tooth disease: recommendations for exercise prescription. Arch Phys Med Rehabil 2004, 85:1217–1223.

    Article  PubMed  Google Scholar 

  16. Chetlin RD, Gutmann L, Tarnopolsky MA, et al.: Resistance training exercise and creatine in patients with Charcot-Marie-Tooth disease. Muscle Nerve 2004, 30:69–76.

    Article  PubMed  CAS  Google Scholar 

  17. Aitkens SG, McCrory MA, Kilmer DD, Bernauer EM: Moderate resistance exercise program: its effects in slowly progressive neuromuscular disease. Arch Phys Med Rehabil 1993, 74:711–715.

    Article  PubMed  CAS  Google Scholar 

  18. Kilmer DD, McCrory MA, Wright NC, et al.: The effect of a high-resistance exercise program in slowly progressive neuromuscular disease. Arch Phys Med Rehabil 1994, 75:560–563.

    PubMed  CAS  Google Scholar 

  19. Videler AJ, Beelen A, Aufdemkampe G, et al.: Hand strength and fatigue in patients with hereditary motor and sensory neuropathy (types I and II). Arch Phys Med Rehabil 2002, 83:1274–1278.

    Article  PubMed  Google Scholar 

  20. Sackley C, Disler PB, Turner-Stokes L, Wade DT: Rehabilitation interventions for foot drop in neuromuscular disease. Cochrane Database Syst Rev 2007, CD003908.

  21. Abresch RT, Carter GT, Jensen MP, Kilmer DD: Assessment of pain and health-related quality of life in slowly progressive neuromuscular disease. Am J Hosp Palliat Care 2002, 19:39–48.

    Article  PubMed  Google Scholar 

  22. Carter GT, Han JJ, Mayadev A, Weiss MD: Modafinil reduces fatigue in Charcot-Marie-Tooth disease: a case series. Am J Hosp Palliat Med 2006, 23:412–416.

    Article  Google Scholar 

  23. Carter GT: Rehabilitation management of peripheral neuropathy. Semin Neurol 2005, 25:229–237.

    Article  PubMed  Google Scholar 

  24. Breslin E, Booth J, Lord B, et al.: Respiratory responses to unsupported arm exercise (UAE) in Charcot-Marie-Tooth (CMT) [abstract]. Am Rev Resp Dis 1993, 147:A532–A533.

    Google Scholar 

  25. Breslin EH, Carter GT, Mercer K, et al.: Fatigue in patients with Charcot-Marie-Tooth. Arch Phys Med Rehabil 1993, 74:1256–1257.

    Article  Google Scholar 

  26. Carter GT, England JD, Chance PF: Charcot-Marie-Tooth disease: electrophysiology, molecular biology, and clinical management [review]. IDrugs 2004, 7:151–159.

    PubMed  CAS  Google Scholar 

  27. Benditt JO: Management of pulmonary complications in neuromuscular disease. Phys Med Rehabil Clin N Am 1998, 9:167–185.

    PubMed  CAS  Google Scholar 

  28. Neijenhuis K, Beynon A, Snik A, et al.: Auditory processing in patients with Charcot-Marie-Tooth disease type 1A. Otol Neurotol 2003, 24:872–877.

    Article  PubMed  Google Scholar 

  29. Papadakis CE, Hajiioannou JK, Kyrmizakis DE, Bizakis JG: Bilateral sudden sensorineural hearing loss caused by Charcot-Marie-Tooth disease. J Laryngol Otol 2003, 117:399–401.

    Article  PubMed  Google Scholar 

  30. Safi GM, Szigeti K, Snipes GJ, et al.: Molecular mechanisms, diagnosis, and rational approaches to management of and therapy for Charcot-Marie-Tooth disease and related peripheral neuropathies. J Investig Med 2003, 51:261–283.

    Article  Google Scholar 

  31. Busiguina S, Fernandez AM, Barrios V, et al.: Neurodegeneration is associated to changes in serum insulin-like growth factors. Neurobiol Dis 2000, 7:657–665.

    Article  PubMed  CAS  Google Scholar 

  32. Sahenk Z, Nagaraja HN, McCracken BS: Neurotrophin-3 promotes nerve regeneration and improvements in sensory function in CMT1A. Results from animal models and a pilot clinical study. Neurology 2005, 65:681–685.

    Article  PubMed  CAS  Google Scholar 

  33. Hodapp JA, Carter GT, Lipe HP, et al.: Double trouble in hereditary neuropathy: concomitant mutations in the PMP-22 gene and another gene produce novel phenotypes. Arch Neurol 2006, 63:112–117.

    Article  PubMed  Google Scholar 

  34. Atanasoski S, Scherer SS, Nave KA, Suter U: Proliferation of Schwann cells and regulation of cyclin D1 expression in an animal model of Charcot-Marie-Tooth disease type 1A. J Neurosci Res 2002, 67:443–449.

    Article  PubMed  CAS  Google Scholar 

  35. Kaya F, Belin S, Bourgeois P, et al.: Ascorbic acid inhibits PMP22 expression by reducing cAMP levels. Neuromuscul Disord 2007, 17:248–253.

    Article  PubMed  Google Scholar 

  36. Khajavi M, Shiga K, Wiszniewski W, et al.: Oral curcumin mitigates the clinical and neuropathologic phenotype of the Trembler-J mouse: a potential therapy for inherited neuropathy. Am J Hum Genet 2007, 81:438–453.

    Article  PubMed  CAS  Google Scholar 

  37. Marco A, Cuesta A, Pedrola L, et al.: Evolutionary and structural analyses of GDAP1, involved in Charcot-Marie-Tooth disease, characterize a novel class of glutathione transferase-related genes. Mol Biol Evol 2003, 2:12–19.

    Google Scholar 

  38. Azzedine H, Ruberg M, Ente D, et al.: Variability of disease progression in a family with autosomal recessive CMT associated with a S194X and new R310Q mutation in the GDAP1 gene. Neuromuscul Disord 2003, 13:341–346.

    PubMed  CAS  Google Scholar 

  39. Stein MP, Dong J, Wandinger-Ness A: Rab proteins and endocytic trafficking: potential targets for therapeutic intervention. Adv Drug Deliv Rev 2003, 55:1421–1437.

    Article  PubMed  CAS  Google Scholar 

  40. Sereda MW, Meyer zu Hörste G, Suter U, et al.: Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat Med 2003, 9:1533–1537.

    Article  PubMed  CAS  Google Scholar 

  41. Carter GT, Ugalde VO: Medical marijuana: emerging applications for the management of neurological disorders. Phys Med Rehabil Clin N Am 2004, 15:943–954.

    PubMed  Google Scholar 

  42. Carter GT, Weydt P: Cannabis: old medicine with new promise for neurological disorders. Curr Opin Investig Drugs 2002, 3:437–440.

    PubMed  CAS  Google Scholar 

  43. Guzman M, Sanchez C, Galve-Roperh I: Control of the cell survival/death decision by cannabinoids. J Mol Med 2001, 78:613–625.

    Article  PubMed  CAS  Google Scholar 

  44. Hampson AJ, Grimaldi M, Axelrod J, et al.: Cannabidiol and (-)Δ9-tetrahydrocannabinol are neuroprotective antioxidants. Proc Natl Acad Sci U S A 1998, 95:8268–8273.

    Article  PubMed  CAS  Google Scholar 

  45. Hampson AJ, Grimaldi M, Lolic M, et al.: Neuroprotective antioxidants from marijuana. Ann N Y Acad Sci 2000, 899:274–282.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Rehabilitation Medicine, University of Washington, Box 356490, 1959 N.E. Pacific Avenue, Seattle, WA, 98195, USA

    Gregory T. Carter

Authors
  1. Gregory T. Carter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michael D. Weiss
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jay J. Han
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Phillip F. Chance
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John D. England
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gregory T. Carter.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Carter, G.T., Weiss, M.D., Han, J.J. et al. Charcot-Marie-Tooth disease. Curr Treat Options Neurol 10, 94–102 (2008). https://doi.org/10.1007/s11940-008-0011-3

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11940-008-0011-3

Keywords

Search

Navigation