Medscape is available in 5 Language Editions – Choose your Edition here.


Physical Medicine and Rehabilitation for Charcot-Marie-Tooth Disease Follow-up

  • Author: Divakara Kedlaya, MBBS; Chief Editor: Robert H Meier, III, MD  more...
Updated: Jan 07, 2016

Further Outpatient Care

Patients should have regular follow-up visits to check for deterioration in function and the development of contractures. This follow-up allows early detection of complications. Proper interventions early in the disease course help to avoid significant and permanent functional limitations.[59]



Regular and proper follow-up and therapeutic interventions are necessary to avoid joint contractures and deformities.[59]

Proper genetic counseling helps parents to understand the risk of having a child with this disorder and gives them a chance to make informed decisions about having children.

Use of Vincristine is clearly contraindicated in patients with known or possible CMT-1A and most likely HNPP. Use of vincristine in other CMT subtypes should be considered with caution. Other agents that have reported to exacerbate CMT-related neuropathy in the Charcot-Marie-Tooth Association (CMTA) database include nitrous oxide, metronidazole, nitrofurantoin, phenytoin, statins and sertraline.[87]



Due to a loss of protective sensation distally in all 4 limbs, patients with Charcot-Marie-Tooth disease (CMT) are susceptible to skin breakdown, burns, nonhealing foot ulcers, and in severe cases, bony, bilateral foot deformities. As mentioned previously, orthoses are required for the treatment of foot drop or to accommodate bony foot deformities. If not fit properly, the orthoses themselves become a source of skin breakdown secondary to associated distal sensory impairment.

Maternal CMT increases the risk for complications during delivery; this risk is linked to a higher occurrence, in such cases, of emergency interventions during birth.



The prognosis for the different types of Charcot-Marie-Tooth disease (CMT) varies; it depends on the condition's clinical severity (see the table under Causes).

Generally, CMT is a slowly progressive neuropathy, with eventual disability occurring secondary to distal muscle weakness and deformities.

CMT usually does not shorten a patient's expected life span.

Shy and colleagues developed the CMT neuropathy score, which is a modification of the total neuropathy score.[88] This has been shown to be a validated measure of length-dependent axonal and demyelinating CMT disability and can be investigated as an end point for longitudinal studies and clinical trials of CMT.

The Inherited Neuropathies Consortium developed an 11-item CMT Pediatric Scale (CMTPedS) to measure impairment of children with CMT. Testing showed the scale to be a reliable, valid, and sensitive global measure of disability for children from the age of 3 years.[89]


Patient Education

Genetic counseling is the process of providing individuals and families with information on the nature, inheritance patterns, and implications of genetic disorders in order to help them make informed medical and personal decisions. Offer patients with Charcot-Marie-Tooth disease (CMT) genetic counseling so that they can make informed decisions regarding the potential risk of passing the disease to their children.[90]

Certain drugs and medications, such as vincristine,[73, 74] isoniazid, paclitaxel, cisplatin, and nitrofurantoin, are known to cause nerve damage and should be avoided.

Routine exercise within the individual's capability is encouraged; many individuals remain physically active.

Obesity should be avoided, because it makes walking more difficult.

Daily heel-cord stretching exercises are warranted to prevent Achilles tendon shortening.

Contributor Information and Disclosures

Divakara Kedlaya, MBBS Clinical Associate Professor, Department of Physical Medicine and Rehabilitation, Loma Linda University School of Medicine; Medical Director, Physical Medicine and Rehabilitation and Pain Management, St Mary Corwin Medical Center

Divakara Kedlaya, MBBS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Colorado Medical Society, American Association of Neuromuscular and Electrodiagnostic Medicine

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Michael T Andary, MD, MS Professor, Residency Program Director, Department of Physical Medicine and Rehabilitation, Michigan State University College of Osteopathic Medicine

Michael T Andary, MD, MS is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, American Association of Neuromuscular and Electrodiagnostic Medicine, American Medical Association, Association of Academic Physiatrists

Disclosure: Received honoraria from Allergan for speaking and teaching.

Chief Editor

Robert H Meier, III, MD Director, Amputee Services of America; Active Medical Staff, Presbyterian/St Luke’s Hospital, Spalding Rehabilitation Hospital, Select Specialty Hospital; Consulting Staff, Kindred Hospital

Robert H Meier, III, MD is a member of the following medical societies: American Academy of Physical Medicine and Rehabilitation, Association of Academic Physiatrists

Disclosure: Nothing to disclose.

Additional Contributors

Milton J Klein, DO, MBA Consulting Physiatrist, Heritage Valley Health System-Sewickley Hospital and Ohio Valley General Hospital

Milton J Klein, DO, MBA is a member of the following medical societies: American Academy of Disability Evaluating Physicians, American Academy of Medical Acupuncture, American Academy of Osteopathy, American Academy of Physical Medicine and Rehabilitation, American Medical Association, American Osteopathic Association, American Osteopathic College of Physical Medicine and Rehabilitation, American Pain Society, Pennsylvania Medical Society

Disclosure: Nothing to disclose.

  1. Dyck PJ, Chance P, Lebo RV. Hereditary motor and sensory neuropathies. Dyck PJ, Thomas PK, Griffen JW, et al, eds. Peripheral Neuropathy. 3rd ed. Saunders; 1993. 1094-136.

  2. Dyck PJ, Karnes JL, Lambert EH. Longitudinal study of neuropathic deficits and nerve conduction abnormalities in hereditary motor and sensory neuropathy type 1. Neurology. 1989 Oct. 39(10):1302-8. [Medline].

  3. Anderson TJ, Klugmann M, Thomson CE, et al. Distinct phenotypes associated with increasing dosage of the PLP gene: implications for CMT1A due to PMP22 gene duplication. Ann N Y Acad Sci. 1999 Sep 14. 883:234-46. [Medline].

  4. Marrosu MG, Vaccargiu S, Marrosu G, et al. A novel point mutation in the peripheral myelin protein 22 (PMP22) gene associated with Charcot-Marie-Tooth disease type 1A. Neurology. 1997 Feb. 48(2):489-93. [Medline].

  5. Suter U, Nave KA. Transgenic mouse models of CMT1A and HNPP. Ann N Y Acad Sci. 1999 Sep 14. 883:247-53. [Medline].

  6. Chapon F, Latour P, Diraison P, Schaeffer S, Vandenberghe A. Axonal phenotype of Charcot-Marie-Tooth disease associated with a mutation in the myelin protein zero gene. J Neurol Neurosurg Psychiatry. 1999 Jun. 66(6):779-82. [Medline]. [Full Text].

  7. Shy ME, Jani A, Krajewski K, et al. Phenotypic clustering in MPZ mutations. Brain. 2004 Feb. 127(Pt 2):371-84. [Medline]. [Full Text].

  8. Nicholson GA. The dominantly inherited motor and sensory neuropathies: clinical and molecular advances. Muscle Nerve. 2006 May. 33(5):589-97. [Medline].

  9. Krajewski KM, Lewis RA, Fuerst DR, et al. Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain. 2000 Jul. 123 Pt 7:1516-27. [Medline]. [Full Text].

  10. Vance JM. Charcot-Marie-Tooth disease type 2. Ann N Y Acad Sci. 1999 Sep 14. 883:42-6. [Medline].

  11. Marrosu MG, Vaccargiu S, Marrosu G, et al. Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. Neurology. 1998 May. 50(5):1397-401. [Medline].

  12. A service of the U.S. National Library of Medicine. Genetics Home Reference: Your reference to understanding genetics conditions. Charcot-Marie-Tooth disease. Published: February 25, 2014. Available at

  13. Kurihara S, Adachi Y, Wada K, et al. An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan. Neuroepidemiology. 2002 Sep-Oct. 21(5):246-50. [Medline].

  14. Morocutti C, Colazza GB, Soldati G, et al. Charcot-Marie-Tooth disease in Molise, a central-southern region of Italy: an epidemiological study. Neuroepidemiology. 2002 Sep-Oct. 21(5):241-5. [Medline].

  15. Braathen GJ. Genetic epidemiology of Charcot-Marie-Tooth disease. Acta Neurol Scand Suppl. 2012. iv-22. [Medline].

  16. Holmes JR, Hansen ST Jr. Foot and ankle manifestations of Charcot-Marie-Tooth disease. Foot Ankle. 1993 Oct. 14(8):476-86. [Medline].

  17. Burns J, Ryan MM, Ouvrier RA. Evolution of foot and ankle manifestations in children with CMT1A. Muscle Nerve. 2009 Feb. 39(2):158-66. [Medline].

  18. Carter GT, Jensen MP, Galer BS, et al. Neuropathic pain in Charcot-Marie-Tooth disease. Arch Phys Med Rehabil. 1998 Dec. 79(12):1560-4. [Medline].

  19. Garcia CA. A clinical review of Charcot-Marie-Tooth. Ann N Y Acad Sci. 1999 Sep 14. 883:69-76. [Medline].

  20. Thomas PK. Overview of Charcot-Marie-Tooth disease type 1A. Ann N Y Acad Sci. 1999 Sep 14. 883:1-5. [Medline].

  21. Auer-Grumbach M, Wagner K, Strasser-Fuchs S, et al. Clinical predominance of proximal upper limb weakness in CMT1A syndrome. Muscle Nerve. 2000 Aug. 23(8):1243-9. [Medline].

  22. Pareyson D, Taroni F, Botti S, et al. Cranial nerve involvement in CMT disease type 1 due to early growth response 2 gene mutation. Neurology. 2000 Apr 25. 54(8):1696-8. [Medline].

  23. van Pomeren M, Selles RW, van Ginneken BT, et al. The hypothesis of overwork weakness in Charcot-Marie-Tooth: a critical evaluation. J Rehabil Med. 2009 Jan. 41(1):32-4. [Medline].

  24. Burns J, Bray P, Cross LA, et al. Hand involvement in children with Charcot-Marie-Tooth disease type 1A. Neuromuscul Disord. 2008 Dec. 18(12):970-3. [Medline].

  25. Pazzaglia C, Vollono C, Ferraro D, Virdis D, Lupi V, Le Pera D. Mechanisms of neuropathic pain in patients with Charcot-Marie-Tooth 1 A: a laser-evoked potential study. Pain. 2010 May. 149(2):379-85. [Medline].

  26. Ribiere C, Bernardin M, Sacconi S, Delmont E, Fournier-Mehouas M, Rauscent H. Pain assessment in Charcot-Marie-Tooth (CMT) disease. Ann Phys Rehabil Med. 2012 Apr. 55(3):160-73. [Medline].

  27. Kousseff BG, Hadro TA, Treiber DL, et al. Charcot-Marie-Tooth disease with sensorineural hearing loss--an autosomal dominant trait. Birth Defects Orig Artic Ser. 1982. 18(3B):223-8. [Medline].

  28. Stojkovic T, Latour P, Vandenberghe A, et al. Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q). Neurology. 1999 Mar 23. 52(5):1010-4. [Medline].

  29. Nelis E, Timmerman V, De Jonghe P, et al. Molecular genetics and biology of inherited peripheral neuropathies: a fast-moving field. Neurogenetics. 1999 Sep. 2(3):137-48. [Medline].

  30. Pareyson D. Charcot-Marie-Tooth disease and related neuropathies: molecular basis for distinction and diagnosis. Muscle Nerve. 1999 Nov. 22(11):1498-509. [Medline].

  31. Bergoffen J, Scherer SS, Wang S, et al. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. 1993 Dec 24. 262(5142):2039-42. [Medline].

  32. Bone LJ, Dahl N, Lensch MW, et al. New connexin32 mutations associated with X-linked Charcot-Marie-Tooth disease. Neurology. 1995 Oct. 45(10):1863-6. [Medline].

  33. Lewis RA. The challenge of CMTX and connexin 32 mutations. Muscle Nerve. 2000 Feb. 23(2):147-9. [Medline].

  34. Nicholson SM, Ressot C, Gomes D, et al. Connexin32 in the peripheral nervous system. Functional analysis of mutations associated with X-linked Charcot-Marie-Tooth syndrome and implications for the pathophysiology of the disease. Ann N Y Acad Sci. 1999 Sep 14. 883:168-85. [Medline].

  35. Chance PF. Overview of hereditary neuropathy with liability to pressure palsies. Ann N Y Acad Sci. 1999 Sep 14. 883:14-21. [Medline].

  36. Ionasescu VV, Ionasescu R, Searby C, et al. Dejerine-Sottas disease with de novo dominant point mutation of the PMP22 gene. Neurology. 1995 Sep. 45(9):1766-7. [Medline].

  37. Ben Othmane K, Hentati F, Lennon F, et al. Linkage of a locus (CMT4A) for autosomal recessive Charcot-Marie-Tooth disease to chromosome 8q. Hum Mol Genet. 1993 Oct. 2(10):1625-8. [Medline].

  38. Bolino A, Muglia M, Conforti FL, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000 May. 25(1):17-9. [Medline].

  39. Gambardella A, Bolino A, Muglia M, et al. Genetic heterogeneity in autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths (CMT4B). Neurology. 1998 Mar. 50(3):799-801. [Medline].

  40. Carter GT, Abresch RT, Fowler WM, et al. Profiles of neuromuscular diseases. Hereditary motor and sensory neuropathy, types I and II. Am J Phys Med Rehabil. 1995 Sep-Oct. 74(5 Suppl):S140-9. [Medline].

  41. Keller MP, Chance PF. Inherited neuropathies: from gene to disease. Brain Pathol. 1999 Apr. 9(2):327-41. [Medline].

  42. Bird TD, Ott J, Giblett ER, et al. Genetic linkage evidence for heterogeneity in Charcot-Marie-Tooth neuropathy (HMSN type I). Ann Neurol. 1983 Dec. 14(6):679-84. [Medline].

  43. Berciano J, Combarros O, Figols J, et al. Hereditary motor and sensory neuropathy type II. Clinicopathological study of a family. Brain. 1986 Oct. 109 ( Pt 5):897-914. [Medline].

  44. Rose KJ, Hiller CE, Mandarakas M, Raymond J, Refshauge K, Burns J. Correlates of functional ankle instability in children and adolescents with Charcot-Marie-Tooth disease. J Foot Ankle Res. 2015. 8:61. [Medline]. [Full Text].

  45. Murphy SM, Laura M, Fawcett K, Pandraud A, Liu YT, Davidson GL. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry. 2012 Jul. 83(7):706-10. [Medline].

  46. Miller LJ, Saporta AS, Sottile SL, Siskind CE, Feely SM, Shy ME. Strategy for genetic testing in Charcot-Marie-disease. Acta Myol. 2011 Oct. 30(2):109-16. [Medline]. [Full Text].

  47. Shaffer LG, Kennedy GM, Spikes AS, et al. Diagnosis of CMT1A duplications and HNPP deletions by interphase FISH: implications for testing in the cytogenetics laboratory. Am J Med Genet. 1997 Mar 31. 69(3):325-31. [Medline].

  48. Nicholson GA. Penetrance of the hereditary motor and sensory neuropathy Ia mutation: assessment by nerve conduction studies. Neurology. 1991 Apr. 41(4):547-52. [Medline].

  49. Hayasaka K, Himoro M, Sato W, et al. Charcot-Marie-Tooth neuropathy type 1B is associated with mutations of the myelin P0 gene. Nat Genet. 1993 Sep. 5(1):31-4. [Medline].

  50. Birouk N, LeGuern E, Maisonobe T, et al. X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study. Neurology. 1998 Apr. 50(4):1074-82. [Medline].

  51. Elliott JL, Kwon JM, Goodfellow PJ, et al. Hereditary motor and sensory neuropathy IIB: clinical and electrodiagnostic characteristics. Neurology. 1997 Jan. 48(1):23-8. [Medline].

  52. England JD, Garcia CA. Electrophysiological studies in the different genotypes of Charcot- Marie-Tooth disease. Curr Opin Neurol. 1996 Oct. 9(5):338-42. [Medline].

  53. Gutierrez A, England JD, Sumner AJ, et al. Unusual electrophysiological findings in X-linked dominant Charcot-Marie-Tooth disease. Muscle Nerve. 2000 Feb. 23(2):182-8. [Medline].

  54. Lewis RA, Sumner AJ. Electrophysiologic features of inherited demyelinating neuropathies: a reappraisal. Ann N Y Acad Sci. 1999 Sep 14. 883:321-35. [Medline].

  55. Quattrone A, Gambardella A, Bono F, et al. Autosomal recessive hereditary motor and sensory neuropathy with focally folded myelin sheaths: clinical, electrophysiologic, and genetic aspects of a large family. Neurology. 1996 May. 46(5):1318-24. [Medline].

  56. Nicholson G, Nash J. Intermediate nerve conduction velocities define X-linked Charcot-Marie- Tooth neuropathy families. Neurology. 1993 Dec. 43(12):2558-64. [Medline].

  57. Bornemann A, Hansen FJ, Schmalbruch H. Nerve and muscle biopsy in a case of hereditary motor and sensory neuropathy type III with basal lamina onion bulbs. Neuropathol Appl Neurobiol. 1996 Feb. 22(1):77-81. [Medline].

  58. Guillebastre B, Calmels P, Rougier PR. Assessment of appropriate ankle-foot orthoses models for patients with Charcot-Marie-Tooth disease. Am J Phys Med Rehabil. 2011 Aug. 90(8):619-27. [Medline].

  59. Njegovan ME, Leonard EI, Joseph FB. Rehabilitation medicine approach to Charcot-Marie-Tooth disease. Clin Podiatr Med Surg. 1997 Jan. 14(1):99-116. [Medline].

  60. Vinci P, Gargiulo P. Poor compliance with ankle-foot-orthoses in Charcot-Marie-Tooth disease. Eur J Phys Rehabil Med. 2008 Mar. 44(1):27-31. [Medline].

  61. Ramdharry GM, Pollard AJ, Marsden JF, Reilly MM. Comparing gait performance of people with Charcot-Marie-Tooth disease who do and do not wear ankle foot orthoses. Physiother Res Int. 2012 Dec. 17(4):191-9. [Medline].

  62. Dufek JS, Neumann ES, Hawkins MC, O'Toole B. Functional and dynamic response characteristics of a custom composite ankle foot orthosis for Charcot-Marie-Tooth patients. Gait Posture. 2014 Jan. 39(1):308-13. [Medline].

  63. Guillebastre B, Calmels P, Rougier PR. Assessment of appropriate ankle-foot orthoses models for patients with Charcot-Marie-Tooth disease. Am J Phys Med Rehabil. 2011 Aug. 90(8):619-27. [Medline].

  64. Phillips MF, Robertson Z, Killen B, White B. A pilot study of a crossover trial with randomized use of ankle-foot orthoses for people with Charcot-Marie-tooth disease. Clin Rehabil. 2012 Jun. 26(6):534-44. [Medline].

  65. Hassel B. Improvement of muscle function in Charcot-Marie-Tooth disease by transcutaneous electric nerve stimulation. Muscle Nerve. 1998 Feb. 21(2):267-8. [Medline].

  66. El Mhandi L, Pichot V, Calmels P, Gautheron V, Roche F, Féasson L. Exercise training improves autonomic profiles in patients with Charcot-Marie-Tooth disease. Muscle Nerve. 2011 Nov. 44(5):732-6. [Medline].

  67. Sman AD, Hackett D, Fiatarone Singh M, Fornusek C, Menezes MP, Burns J. Systematic review of exercise for Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2015 May 22. [Medline].

  68. Kamholz J, Menichella D, Jani A, et al. Charcot-Marie-Tooth disease type 1: molecular pathogenesis to gene therapy. Brain. 2000 Feb. 123 ( Pt 2):222-33. [Medline]. [Full Text].

  69. Gess B, Baets J, De Jonghe P, Reilly MM, Pareyson D, Young P. Ascorbic acid for the treatment of Charcot-Marie-Tooth disease. Cochrane Database Syst Rev. 2015 Dec 11. 12:CD011952. [Medline].

  70. Hoff JM, Gilhus NE, Daltveit AK. Pregnancies and deliveries in patients with Charcot-Marie-Tooth disease. Neurology. 2005 Feb 8. 64(3):459-62. [Medline].

  71. Ward CM, Dolan LA, Bennett DL, et al. Long-term results of reconstruction for treatment of a flexible cavovarus foot in Charcot-Marie-Tooth disease. J Bone Joint Surg Am. 2008 Dec. 90(12):2631-42. [Medline]. [Full Text].

  72. Wukich DK, Bowen JR. A long-term study of triple arthrodesis for correction of pes cavovarus in Charcot-Marie-Tooth disease. J Pediatr Orthop. 1989 Jul-Aug. 9(4):433-7. [Medline].

  73. Graf WD, Chance PF, Lensch MW, et al. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996 Apr 1. 77(7):1356-62. [Medline].

  74. Kuruvilla G, Perry S, Wilson B, et al. The natural history of vincristine-induced laryngeal paralysis in children. Arch Otolaryngol Head Neck Surg. 2009 Jan. 135(1):101-5. [Medline].

  75. Dyck PJ, Swanson CJ, Low PA, et al. Prednisone-responsive hereditary motor and sensory neuropathy. Mayo Clin Proc. 1982 Apr. 57(4):239-46. [Medline].

  76. Ginsberg L, Malik O, Kenton AR, et al. Coexistent hereditary and inflammatory neuropathy. Brain. 2004 Jan. 127:193-202. [Medline]. [Full Text].

  77. Sahenk Z, Nagaraja HN, McCracken BS, King WM, Freimer ML, Cedarbaum JM, et al. NT-3 promotes nerve regeneration and sensory improvement in CMT1A mouse models and in patients. Neurology. 2005 Sep 13. 65(5):681-9. [Medline].

  78. Pareyson D, Marchesi C. Natural history and treatment of peripheral inherited neuropathies. Adv Exp Med Biol. 2009. 652:207-24. [Medline].

  79. Passage E, Norreel JC, Noack-Fraissignes P, et al. Ascorbic acid treatment corrects the phenotype of a mouse model of Charcot-Marie-Tooth disease. Nat Med. 2004 Apr. 10(4):396-401. [Medline].

  80. Burns J, Ouvrier RA, Yiu EM, Joseph PD, Kornberg AJ, Fahey MC, et al. Ascorbic acid for Charcot-Marie-Tooth disease type 1A in children: a randomised, double-blind, placebo-controlled, safety and efficacy trial. Lancet Neurol. 2009 Jun. 8(6):537-44. [Medline].

  81. Micallef J, Attarian S, Dubourg O, Gonnaud PM, Hogrel JY, Stojkovic T, et al. Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Neurol. 2009 Dec. 8(12):1103-10. [Medline].

  82. Verhamme C, de Haan RJ, Vermeulen M, Baas F, de Visser M, van Schaik IN. Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial. BMC Med. 2009 Nov 12. 7:70. [Medline]. [Full Text].

  83. Pareyson D, Reilly MM, Schenone A, Fabrizi GM, Cavallaro T, Santoro L, et al. Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial. Lancet Neurol. 2011 Apr. 10(4):320-8. [Medline]. [Full Text].

  84. Meyer zu Horste G, Prukop T, Liebetanz D, Mobius W, Nave KA, Sereda MW. Antiprogesterone therapy uncouples axonal loss from demyelination in a transgenic rat model of CMT1A neuropathy. Ann Neurol. 2007 Jan. 61(1):61-72. [Medline].

  85. Sereda MW, Meyer zu Hörste G, Suter U, Uzma N, Nave KA. Therapeutic administration of progesterone antagonist in a model of Charcot-Marie-Tooth disease (CMT-1A). Nat Med. 2003 Dec. 9(12):1533-7. [Medline].

  86. Shy ME. Charcot-Marie-Tooth disease: an update. Curr Opin Neurol. 2004 Oct. 17(5):579-85. [Medline].

  87. Weimer LH, Podwall D. Medication-induced exacerbation of neuropathy in Charcot Marie Tooth disease. J Neurol Sci. 2006 Mar 15. 242(1-2):47-54. [Medline].

  88. Shy ME, Blake J, Krajewski K, et al. Reliability and validity of the CMT neuropathy score as a measure of disability. Neurology. 2005 Apr 12. 64(7):1209-14. [Medline].

  89. Burns J, Ouvrier R, Estilow T, Shy R, Laurá M, Pallant JF, et al. Validation of the Charcot-Marie-Tooth disease pediatric scale as an outcome measure of disability. Ann Neurol. 2012 May. 71(5):642-52. [Medline]. [Full Text].

  90. Siskind CE, Panchal S, Smith CO, Feely SM, Dalton JC, Schindler AB, et al. A review of genetic counseling for Charcot Marie Tooth disease (CMT). J Genet Couns. 2013 Aug. 22(4):422-36. [Medline].

Foot deformities in a 16-year-old boy with Charcot-Marie-Tooth disease type 1A.
Charcot-Marie-Tooth disease type 1A DNA test showing duplication in the short arm of chromosome 17 (A) compared with normal (B).
Nerve conduction study showing decreased nerve conduction velocity in the median nerve in an 18-year-old woman with Charcot-Marie-Tooth disease type 1.
Foot of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Hands of 29-year-old with advanced Charcot-Marie-Tooth disease type 1.
Right ulnar motor nerve conduction study in a 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.
Left ulnar motor nerve conduction study in 29-year-old patient with advanced Charcot-Marie-Tooth disease type 1.
Table. Charcot-Marie-Tooth Disorders: Genetic and Clinical Feature Comparison
CMT Type Chromosome; Inheritance Pattern Age of Onset Clinical Features Average NCVs§
CMT-1A (PMP-22 dupl.) 17p11.2; AD* First decade Distal weakness 15-20 m/s
CMT-1B (P0 -MPZ)** 1q23.3; AD First decade Distal weakness < 20 m/s
CMT-1C (non-A, non-B) (LITAF) 16p13.13;AD Second decade Distal weakness 26-42 m/s
CMT-1D (EGR-2)# 10q21.3; AD First decade Distal weakness 15-20 m/s
CMT-1E (PMP22) 17p11.2; AD First decade Distal weakness, deafness 15-20 m/s
CMT-1F (NEFL) 8p21.2; AD First decade Distal weakness 15-20 m/s
CMT-X (connexin-32)[31, 32, 33, 34] Xq13; XD Second decade Distal weakness 25-40 m/s
CMT-2A 1p36; AD 10 y Distal weakness >38 m/s
CMT-2B 3q21; AD Second decade Distal weakness,

sensory loss, skin ulcers

Axon loss; Normal
CMT-2C 12q23-q24, AD First decade Vocal cord, diaphragm, and

distal weakness

>50 m/s
CMT-2D 7p14; AD 16-30 y Distal weakness, upper limb predominantly Axon loss; N††
CMT-2E 8p21; AD 10-30 y Distal weakness, lower limb predominantly Axon loss; N
CMT-2F 7q11-q21; AD 15-25 y Distal weakness Axon loss; N
CMT-2G 12q12-q13; AD 9-76 y Distal weakness Axon loss; N
CMT-2H 8q21; AD 15-25 y Distal weakness, pyramidal features Axon loss; N
CMT-2I 1q23; AD 47-60 y Distal weakness Axon loss; N
CMT-2J 1q23; AD 40-50 y Distal weakness, hearing loss Axon loss; N
CMT-2K 8q13-q21; AD < 4 y Distal weakness Axon loss; N
CMT-2L 12q24; AD 15-25 y Distal weakness Axon loss; N
CMT–R-Ax (Ouvrier) AR First decade Distal weakness Axon loss; N
CMT–R-Ax (Moroccan) 1q21; AR Second decade Distal weakness Axon loss; N
Cowchock syndrome Xq24-q26 First decade Distal weakness, deafness, mental retardation Axon loss; N
HNPP|| (PMP-22 deletion)[35]

or tomaculous neuropathy

17p11; AD All ages Episodic weakness and numbness Conduction Blocks
Dejerine-Sottas-syndrome (DSS) or HMSN-3[36] P0; AR

PMP-22; AD

8q23; AD

2 y Severe weakness < 10 m/s

hypomyelination (CH)

P0, EGR-2 or PMP-22


Birth Severe weakness < 10 m/s
CMT-4A[37] 8q13; AR Childhood Distal weakness Slow

(myotubularin- related

protein 2)[38, 39]

11q23; AR 2-4 y Distal and proximal


CMT-4C 5q23; AR 5-15 y Delayed walking 14-32 m/s
CMT-4D (Lom)

(N-myc downstream-

regulated gene 1)

8q24; AR 1-10 y Distal muscle wasting, foot and hand deformities 10-20 m/s
CMT-4E (EGR-2) 10q21; AR Birth Infant hypotonia 9-20 m/s
CMT-4G 10q23.2; AR 8-16 years Distal weakness 9-20 m/s
CMT-4H 12p11.21-q13.11; AR 0-2 years Delayed walking 9-20 m/s
CMT-4F 19q13; AR 1-3 y Motor delay Absent
*Autosomal dominant

†Autosomal recessive

‡X-linked dominant

§Nerve conduction velocities

||Hereditary neuropathy with liability to pressure palsy

¶Peripheral myelin protein

#Early growth response

**Myelin protein zero


All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.