Highlights & Basics
- Charcot-Marie-Tooth (CMT) disease comprises a group of hereditary peripheral neuropathies with different genetic abnormalities.
- Absence of a family history does not rule out the condition.
- Key features include clumsiness as a child, weak ankles, symmetrical nerve conduction changes, and a steppage gait (lifting legs up excessively to clear the toes).
- Pes cavus (high foot arches with hammertoes) and distal atrophy of the hands and legs are characteristic.
- Genetic testing should be carefully considered.
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Citations
Saporta AS, Sottile SL, Miller LJ, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol. 2011 Jan;69(1):22-33.[Abstract]
Shy M, Lupski JR, Chance PF, et al. The hereditary motor and sensory neuropathies: an overview of the clinical, genetic, electrophysiologic and pathologic features. In: Dyck PJ, ed. Peripheral neuropathy. Vol 2. 4th ed. Philadelphia, PA: WB Saunders; 2005:1623-58.
Yiu EM, Bray P, Baets J, et al. Clinical practice guideline for the management of paediatric Charcot-Marie-Tooth disease. J Neurol Neurosurg Psychiatry. 2022 May;93(5):530-8.[Abstract][Full Text]
Murphy SM, Laura M, Fawcett K, et al. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry. 2012 Jul;83(7):706-10.[Abstract]
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5. Dubourg O, Tardieu S, Birouk N, et al. The frequency of 17p11.2 duplication and Connexin 32 mutations in 282 Charcot-Marie-Tooth families in relation to the mode of inheritance and motor nerve conduction velocity. Neuromuscul Disord. 2001 Jul;11(5):458-63.[Abstract]
6. Meretoja P, Silander K, Kalimo H, et al. Epidemiology of hereditary neuropathy with liability to pressure palsies (HNPP) in south western Finland. Neuromuscul Disord. 1997 Dec;7(8):529-32.[Abstract]
7. Saporta AS, Sottile SL, Miller LJ, et al. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol. 2011 Jan;69(1):22-33.[Abstract]
8. Shy M, Lupski JR, Chance PF, et al. The hereditary motor and sensory neuropathies: an overview of the clinical, genetic, electrophysiologic and pathologic features. In: Dyck PJ, ed. Peripheral neuropathy. Vol 2. 4th ed. Philadelphia, PA: WB Saunders; 2005:1623-58.
9. 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.[Abstract]
10. Murphy SM, Herrmann DN, McDermott MP, et al. Reliability of the CMT neuropathy score (second version) in Charcot-Marie-Tooth disease. J Peripher Nerv Syst. 2011 Sep;16(3):191-8.[Abstract][Full Text]
11. Fridman V, Sillau S, Acsadi G, et al. A longitudinal study of CMT1A using Rasch analysis based CMT neuropathy and examination scores. Neurology. 2020 Mar 3;94(9):e884-e896.[Abstract][Full Text]
12. Hoogendijk JE, Hensels GW, Gabreels-Festen AA, et al. De-novo mutation in hereditary motor and sensory neuropathy type 1. Lancet. 1992 May 2;339(8801):1081-2.[Abstract]
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15. England JD, Gronseth GS, Franklin G, et al. Practice parameter: evaluation of distal symmetric polyneuropathy: role of laboratory and genetic testing (an evidence-based review). Neurology. 2009 Jan 13;72(2):185-92.[Abstract][Full Text]
16. Murphy SM, Laura M, Fawcett K, et al. Charcot-Marie-Tooth disease: frequency of genetic subtypes and guidelines for genetic testing. J Neurol Neurosurg Psychiatry. 2012 Jul;83(7):706-10.[Abstract]
17. Szigeti K, Garcia CA, Lupski JR. Charcot Marie Tooth disease and related hereditary polyneuropathies: molecular diagnostics determine aspects of medical management. Genet Med. 2006 Feb;8(2):86-92.[Abstract]
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19. Abdelnaby R, Elgenidy A, Sonbol YT, et al. Nerve sonography in Charcot-Marie-Tooth disease: a systematic review and meta-analysis of 6061 measured nerves. Ultrasound Med Biol. 2022 Aug;48(8):1397-409.[Abstract]
20. Duchesne M, Mathis S, Richard L, et al. Nerve biopsy is still useful in some inherited neuropathies. J Neuropathol Exp Neurol. 2018 Feb 1;77(2):88-99.[Abstract][Full Text]
21. Korinthenberg R, Trollmann R, Plecko B, et al. Differential diagnosis of acquired and hereditary neuropathies in children and adolescents-consensus-based practice guidelines. Children (Basel). 2021 Aug 9;8(8):687.[Abstract][Full Text]
22. Borry P, Stultiens L, Nys H, et al. Presymptomatic and predictive genetic testing in minors: a systematic review of guidelines and position papers. Clin Genet. 2006 Nov;70(5):374-81.[Abstract]
23. El Mhandi L, Millet GY, Calmels P, et al. Benefits of interval-training on fatigue and functional capacities in Charcot-Marie-Tooth disease. Muscle Nerve. 2008 May;37(5):601-10.[Abstract]
24. Karas MA, Hoy DJ. Compensatory midfoot dorsiflexion in the individual with heelcord tightness: implications for orthotic device designs. JPO. 2002;14:82-93.[Full Text]
25. Zuccarino R, Anderson KM, Shy ME, et al. Satisfaction with ankle foot orthoses in individuals with Charcot-Marie-Tooth disease. Muscle Nerve. 2021 Jan;63(1):40-5.[Abstract][Full Text]
26. Rose KJ, Burns J, Wheeler DM, et al. Interventions for increasing ankle range of motion in patients with neuromuscular disease. Cochrane Database Syst Rev. 2010;(2):CD006973.[Abstract][Full Text]
27. Pfeffer GB, Gonzalez T, Brodsky J, et al. A Consensus Statement on the Surgical Treatment of Charcot-Marie-Tooth Disease. Foot Ankle Int. 2020 Jul;41(7):870-80.[Abstract]
28. 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.[Abstract]
29. An T, Schwartz E, Kissen M, et al. Safety and efficacy of postoperative indwelling popliteal nerve catheters for outpatient Charcot-Marie-Tooth surgery. Foot Ankle Int. 2022 Apr;43(4):504-8.[Abstract]
30. Novais EN, Kim YJ, Carry PM, et al. Periacetabular osteotomy redirects the acetabulum and improves pain in Charcot-Marie-Tooth hip dysplasia with higher complications compared with developmental dysplasia of the hip. J Pediatr Orthop. 2016 Dec;36(8):853-9.[Abstract]
31. Guyton GP, Mann RA. The pathogenesis and surgical management of foot deformity in Charcot-Marie-Tooth disease. Foot Ankle Clin. 2000 Jun;5(2):317-26.[Abstract]
32. Sheth S, Francies K, Siskind CE, et al. Diabetes mellitus exacerbates motor and sensory impairment in CMT1A. J Peripher Nerv Syst. 2008 Dec;13(4):299-304.[Abstract]
33. Cavaletti G, Forsey K, Alberti P. Toxic medications in Charcot-Marie-Tooth patients: a systematic review. J Peripher Nerv Syst. 2023 Sep;28(3):295-307.[Abstract][Full Text]
34. Burns J, Landorf KB, Ryan MM, et al. Interventions for the prevention and treatment of pes cavus. Cochrane Database Syst Rev. 2007;(4):CD006154.[Abstract][Full Text]
35. Attarian S, Vallat JM, Magy L, et al. An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone, and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A. Orphanet J Rare Dis. 2014 Dec 18;9:199.[Abstract][Full Text]
36. ClinicalTrials.gov. Phase III trial assessing the efficacy and safety of PXT3003 in CMT1A patients (PLEO-CMT): NCT02579759. January 2018 [internet publication].[Full Text]
37. Zhao HT, Damle S, Ikeda-Lee K, et al. PMP22 antisense oligonucleotides reverse Charcot-Marie-Tooth disease type 1A features in rodent models. J Clin Invest. 2018 Jan 2;128(1):359-68.[Abstract][Full Text]
38. Boutary S, Echaniz-Laguna A, Adams D, et al. Treating PMP22 gene duplication-related Charcot-Marie-Tooth disease: the past, the present and the future. Transl Res. 2021 Jan;227:100-11.[Abstract]
39. ClinicalTrials.gov. Phase I/IIa trial of scAAV1.tMCK.NTF3 for treatment of CMT1A. ClinicalTrials.gov Identifier: NCT03520751. Mar 2023 [internet publication].[Full Text]
40. Beloribi-Djefaflia S, Attarian S. Treatment of Charcot-Marie-Tooth neuropathies. Rev Neurol (Paris). 2023 Jan-Feb;179(1-2):35-48.[Abstract]
41. Pons N, Fernández-Eulate G, Pegat A, et al. SORD-related peripheral neuropathy in a French and Swiss cohort: clinical features, genetic analyses, and sorbitol dosages. Eur J Neurol. 2023 Jul;30(7):2001-11.[Abstract][Full Text]
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44. Feely SM, Laura M, Siskind CE, et al. MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology. 2011 May 17;76(20):1690-6.[Abstract][Full Text]
45. Moulin D, Boulanger A, Clark AJ, et al. Pharmacological management of chronic neuropathic pain: revised consensus statement from the Canadian Pain Society. Pain Res Manag. 2014 Nov-Dec;19(6):328-35.[Abstract][Full Text]
46. 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.[Abstract]
