eMedicine Specialties > Neurology > Neuromuscular Diseases

Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies: Differential Diagnoses & Workup

Author: Timothy C Parsons, MD, Fellow in EMG and Neuromuscular Disease, Department of Neurology, Columbia University Medical Center, New York
Coauthor(s): Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York
Contributor Information and Disclosures

Updated: Nov 5, 2009

Differential Diagnoses

Other Problems to Be Considered

The differential diagnosis of neuropathy is wide. A positive family history makes CMT likely, and a pedigree can help elucidate the inheritance pattern, which can narrow the differential diagnosis between CMT subtypes. Nerve conduction velocities, in most cases, can separate CMT1 (very slow) from CMT2 (mildly slow to normal).
 
It is essential to separate the demyelinating forms of CMT from acquired, potentially treatable demyelinating neuropathies. Uniform conduction slowing is seen in CMT1, whereas in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and other immune-mediated neuropathies, conduction velocity varies between segments in the same nerve and different nerves. The Guillain-Barre syndrome has similar electrodiagnostic findings to CIDP but the rapidity of onset that defines the disease should prevent confusion.
 
Other inherited neuropathic syndromes, such as Friedreich Ataxia and Spinal Muscular Atrophy, can be confused with CMT or have overlapping features.
 
Other causes of acquired neuropathy should not be overlooked. Neuropathy may be due to diabetes mellitus or other metabolic/nutritional causes, drugs of abuse such as alcohol, neurotoxic medications, infections (including leprosy, which may cause thickened, palpable nerves), compression, or vasculitis, among others.

Myopathies and muscular dystrophies can be clinically confused with CMT in some cases.

Workup

Laboratory Studies

The workup should be primarily geared toward the identification or exclusion of a treatable neuropathy, including tests that address the causes of neuropathy. If a clear family history is identified and CMT has not been confirmed genetically, genotyping is warranted. Ascertaining the presence of a demyelinating or axonal form with nerve conduction studies, and establishing inheritance pattern with a pedigree can narrow the differential diagnosis and reduce the number of needed tests. De novo mutations are not rare, and genetic counseling can be pursued even in the absence of a family history of neuropathy.
 
Despite the lack of available treatments, genotyping is useful in providing information for prognosis and genetic counseling.
 
A negative genetic test does not exclude the diagnosis, especially in axonal forms. Beinfait and colleagues found mutations in only 3 out of 18 families (61 patients) with CMT2, and Bennett and colleagues found no mutations in 6 families with late-onset (median age 57), predominantly axonal neuropathies.67,79

Imaging Studies

Nerve root hypertrophy can be directly imaged with an MRI of the spine, which may help in distinguishing hereditary from acquired demyelinating neuropathy.80 Sonography of peripheral nerves can play a similar role.81

Other Tests

Examination of the CSF is usually normal except for an elevated CSF protein. More marked elevations of protein are routinely seen in Dejerine-Sottas syndrome and may be more common in forms of CMT with MPZ mutations.4,82,42

Procedures

Electrodiagnostic studies are critical to narrow the differential diagnosis.
 
Harding and Thomas found median nerve conduction velocities below 38 m/s in patients with CMT1 and above 38 m/s in patients with CMT2.64 Thomas and colleagues found median nerve conduction velocities averaged 19.9 m/s and ranged from 5-34 m/s in patients with CMT1. Values in the lower limb nerves were more difficult to obtain because of denervation of small foot muscles, but peroneal and tibial nerve conduction velocity averaged 17 m/sec and ranged between 10-22 m/sec. Sensory nerve action potentials were usually absent or severely reduced in amplitude, but when present, showed similar reductions in velocity (mean 22.9 m/sec).63 Dyck and Lambert had previously shown that ulnar nerve conduction velocities were even more severely affected in patients with Dejerine-Sottas syndrome, consistently measuring less than 10 m/s.4,82  
 
Lewis and Sumner compared 18 patients with CMT1 to 40 patients with chronic acquired demyelinating neuropathies, and found that slowing was uniform both along individual nerves and between different nerves in an individual patient with CMT1. There was no evidence of dispersion or conduction block in any of these patients. They concluded that this pattern serves to distinguish patients with CMT1 from patients with CIDP or AIDP, who demonstrate more multifocality. These findings were confirmed in a larger study of 129 patients with CMT1.83,84

Female carriers with CMTX often demonstrate intermediate nerve conduction velocities, averaging 45 m/sec (ranging from 26-61 m/sec), which is significantly faster than CMT1A. Affected men, by comparison, have slower conduction velocities, averaging 31 m/sec, also significantly higher than those found in CMT1. The combination of intermediate conduction velocities and more rapid velocities in affected females suggests CMTX.74 Interestingly, Dubourg and colleagues found that the difference between the median and ulnar motor nerve conduction velocities in affected female patients differed significantly when compared to the uniform velocities found in CMT1 and healthy subjects. Men with CMTX also demonstrated uniform slowing.47

Histologic Findings

CMT1
 
Dyck and Lambert observed an abnormally large transverse fascicular area in biopsied nerves, but a reduction in the number of myelinated fibers both per unit of fascicular area and per nerve. Large onion bulbs were seen, and there was marked variation in length and diameter of myelinated fiber internodes on teased fiber preparations, indicating chronic demyelination and remyelination. There was additional evidence of Wallerian degeneration in some nerve fibers, indicating concurrent axonal injury.4
 
CMT1A
 
Sural nerve biopsies in patients with confirmed PMP22 duplications show nerve thickening and a reduction in myelinated fiber density even in the first year of life. As the first few years pass, active demyelination is prominent and onion bulbs are infrequent. By late childhood, active demyelination subsides and well-formed onion bulbs appear. There is loss of large fibers and a relative increase in small fibers as a result of regeneration of damaged axons.85
 
CMT2
 
Behse and Buchthal demonstrated endoneurial areas to be normal. Onion bulbs were absent, and segmental demyelination was absent or rare on teased fiber analysis. The main abnormality was a reduction in the number of large fibers.86
 
CMTX
 
Pathology of CMTX is mixed, as would be expected from electrophysiologic data. Hahn and colleagues found mild to moderate degeneration and loss of myelinated nerve fibers. Remaining fibers were surrounded by the thin myelin sheaths that would be expected with either repaired demyelination or regenerated nerve fibers. There were clusters of small fibers, indicating attempts at sprouting as part of the regenerative process. Teased fibers showed evidence of myelin instability in paranodal regions.46

More on Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies

Overview: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Differential Diagnoses & Workup: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Treatment & Medication: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
Follow-up: Charcot-Marie-Tooth and Other Hereditary Motor and Sensory Neuropathies
References
[ CLOSE WINDOW ]

References

  1. Charcot JM. Sur une forme particulaire d'atrophie musculaire progressive souvent familial debutant par les pieds et les jambes et atteingnant plus tard les mains. Rev Med. 1886;6:97-138.

  2. Tooth HH. The peroneal type of progressive muscular atrophy. London: Lewis. 1886.

  3. Dejerine H, Sottas J. Sur la nevrite interstitielle, hypertrophique et progressive de l'enfance. CR Soc Biol (Paris). 1893;45:63-96.

  4. Dyck PJ, Lambert EH. Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. I. Neurologic, genetic, and electrophysiologic findings in hereditary polyneuropathies. Arch Neurol. Jun 1968;18(6):603-18. [Medline].

  5. Thomas PK, Calne DB. Motor nerve conduction velocity in peroneal muscular atrophy: evidence for genetic heterogeneity. J Neurol Neurosurg Psychiatry. Jan 1974;37(1):68-75. [Medline].

  6. Buchthal F, Behse F. Peroneal muscular atrophy (PMA) and related disorders. I. Clinical manifestations as related to biopsy findings, nerve conduction and electromyography. Brain. Mar 1977;100 Pt 1:41-66. [Medline].

  7. Dyck PJ. Inherited neuronal degeneration and atrophy affecting peripheral motor, sensory and autonomic neurons. In: Dyck PJ, Thomas PK, and Lambert EH. Peripheral Neuropathy. 2. 1. Philadelphia: Saunders; 1975:825-867.

  8. Bird TD, Ott J, Giblett ER. Evidence for linkage of Charcot-Marie-Tooth neuropathy to the Duffy locus on chromosome 1. Am J Hum Genet. May 1982;34(3):388-94. [Medline].

  9. Vance JM, Nicholson GA, Yamaoka LH, Stajich J, Stewart CS, Speer MC, et al. Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17. Exp Neurol. May 1989;104(2):186-9. [Medline].

  10. Lupski JR, de Oca-Luna RM, Slaugenhaupt S. DNA duplication associated with Charcot-Marie-Tooth Disease Type 1A. Cell. 1991;66:219-32.

  11. Raeymaekers P, Timmerman V, Nelis E, et al. Duplication in chromosome 17p11.2 in Charcot-Marie-Tooth neuropathy type 1a (CMT1a). Neuromuscul Disord. 1991;1:93-7.

  12. Lupski JR, Wise CA, Kuwano A, Pentao L, Parke JT, Glaze DG. Gene dosage is a mechanism for Charcot-Marie-Tooth disease type 1A. Nat Genet. Apr 1992;1(1):29-33. [Medline].

  13. Wise CA, Garcia CA, Davis SN, Heju Z, Pentao L, Patel PI. Molecular analyses of unrelated Charcot-Marie-Tooth (CMT) disease patients suggest a high frequency of the CMTIA duplication. Am J Hum Genet. Oct 1993;53(4):853-63. [Medline].

  14. Fernandez-Torre JL, Otero B, Alvarez V, Hernando I, Fernandez-Toral J. De novo partial duplication of 17p associated with Charcot-Marie-Tooth disease type 1A. J Neurol Neurosurg Psychiatry. 2001;70:703-4.

  15. Hayasaka K, Himoro M, Sato W, et al. CMT neuropathy 1B is associated with mutations of the myelin P0 gene. Nat Genet. 1993;5:31-4.

  16. Kulkens T, Bolhuis PA, Wolterman RA, Kemp S, te Nijenhuis S, Valentijn LJ. Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B. Nat Genet. Sep 1993;5(1):35-9. [Medline].

  17. Su Y, Brooks DG, Li L, Lepercq J, Trofatter JA, Ravetch JV, et al. Myelin protein zero gene mutated in Charcot-Marie-tooth type 1B patients. Proc Natl Acad Sci U S A. Nov 15 1993;90(22):10856-60. [Medline].

  18. Bergoffen J, Scherer SS, Wang S, Scott MO, Bone LJ, Paul DL. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. Dec 24 1993;262(5142):2039-42. [Medline].

  19. Chance PF, Alderson MK, Leppig KA, Lensch MW, Matsunami N, Smith B. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. Jan 15 1993;72(1):143-51. [Medline].

  20. Warner LE, Hilz MJ, Appel SH, et al. Clinical phenotypes of different MPZ (P-O) mutations may include Charcot-Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. Neuron. 1996;17:451-60.

  21. Marrosu MG, Vaccargiu S, Marrosu G, Vannelli A, Cianchetti C, Muntoni F. Charcot-Marie-Tooth disease type 2 associated with mutation of the myelin protein zero gene. Neurology. May 1998;50(5):1397-401. [Medline].

  22. Numakura C, Shirahata E, Yamashita S, et al. Screening of the early growth response 2 gene in Japanese patients with Charcot–Marie–Tooth disease type 1. J Neurol Sci. 2003;210:61– 64.

  23. Roa BB, Dyck PJ, Marks HG, Chance PF, Lupski JR. Dejerine –Sottas syndrome associated with point mutation in the peripheral myelin protein 22 (PMP22) gene. Nat Genet. 1993;5:269– 73.

  24. Bradley WG, Madrid R, and Davis, CJF . The peroneal muscular atrophy syndrome. Clinical, genetic, electrophysiological, and nerve biopsy studies. III. Clinical, electrophysiological, and pathological correlations. J Neurol Sci. 1977;32:123-36.

  25. Madrid R, Bradley WG, and Davis, CJF. The peroneal muscular atrophy syndrome. Clinical, genetic, electrophysiological, and nerve biopsy studies. II. Observations on pathological changes in sural nerve biopsies. J Neurol Sci. 1977;32:91-122.

  26. Davis CJ, Bradley WG, Madrid R. The peroneal muscular atrophy syndrome: clinical, genetic, electrophysiological and nerve biopsy studies. I. Clinical, genetic and electrophysiological findings and classification. J Genet Hum. Dec 1978;26(4):311-49. [Medline].

  27. Brust JCM, Lovelace RE, and Devi S. Clinical and electrodiagnostic features of Charcot-Marie-Tooth syndrome. Acta Neurologica Scandinavica. 1978;58:Supplement 68: 1-42.

  28. Rossi A, Paradiso C, Cioni R, Rizzuto N, Guazzi G. Charcot-Marie-Tooth disease: study of a large kinship with an intermediate form. J Neurol. 1985;232(2):91-8. [Medline].

  29. Villanova M, Timmerman V, De Jonghe P, Malandrini A, Rizzuto N, Van Broeckhoven C, et al. Charcot-Marie-Tooth disease: an intermediate form. Neuromuscul Disord. Aug 1998;8(6):392-3. [Medline].

  30. Hai M, Bidichandani SI, Patel PI. Identification of a positive regulatory element in the myelin-specific promoter of the PMP22 gene. J Neurosci Res. Sep 15 2001;65(6):508-19. [Medline].

  31. Snipes GJ, Suter U, Welcher A, Shooter E. Characterization of a Novel Peripheral Nervous System Myelin Protein (PMP22/SR13). J Cell Bio. 1992;117:225-238.

  32. Vallat JM, Sindou P, Preux PM, Tabaraud F, Milor AM, Couratier P. Ultrastructural PMP22 expression in inherited demyelinating neuropathies. Ann Neurol. Jun 1996;39(6):813-7. [Medline].

  33. Müller HW. New vistas on the pathomechanism of Charcot-Marie-Tooth and related peripheral neuropathies. Ann N Y Acad Sci. Sep 14 1999;883:152-9. [Medline].

  34. Gabreëls-Festen AA, Joosten EM, Gabreëls FJ, Jennekens FG, Janssen-van Kempen TW. Early morphological features in dominantly inherited demyelinating motor and sensory neuropathy (HMSN type I). J Neurol Sci. Feb 1992;107(2):145-54. [Medline].

  35. García A, Combarros O, Calleja J, Berciano J. Charcot-Marie-Tooth disease type 1A with 17p duplication in infancy and early childhood: a longitudinal clinical and electrophysiologic study. Neurology. Apr 1998;50(4):1061-7. [Medline].

  36. Krajewski KM, Lewis RA, Fuerst DR, Turansky C, Hinderer SR, Garbern J. Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain. Jul 2000;123 ( Pt 7):1516-27. [Medline].

  37. Nodera H, Bostock H, Kuwabara S, Sakamoto T, Asanuma K, Jia-Ying S, et al. Nerve excitability properties in Charcot-Marie-Tooth disease type 1A. Brain. Jan 2004;127:203-11. [Medline].

  38. Giese KP, Martini R, et al. Mouse PO Gene Disruption Leads to Hypomyelination, Abnormal Expression of Recognition Molecules, and Degeneration of Myelin and Axons. Cell. 1991;71:565-576.

  39. Nelis E, Haites N, Van Broeckhoven C. Mutations in the peripheral myelin genes and associated genes in inherited peripheral neuropathies. Hum Mutat. 1999;13(1):11-28. [Medline].

  40. Shy ME, Jáni A, Krajewski K, Grandis M, Lewis RA, Li J. Phenotypic clustering in MPZ mutations. Brain. Feb 2004;127(Pt 2):371-84. [Medline].

  41. Boerkoel CF, Takashima H, Garcia CA, Olney RK, Johnson J, Berry K. Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation. Ann Neurol. Feb 2002;51(2):190-201. [Medline].

  42. Hattori N, Yamamoto M, Yoshihara T, Koike H, Nakagawa M, Yoshikawa H. Demyelinating and axonal features of Charcot-Marie-Tooth disease with mutations of myelin-related proteins (PMP22, MPZ and Cx32): a clinicopathological study of 205 Japanese patients. Brain. Jan 2003;126(Pt 1):134-51. [Medline].

  43. Shy ME. Peripheral neuropathies caused by mutations in the myelin protein zero. J Neurol Sci. Mar 15 2006;242(1-2):55-66. [Medline].

  44. Bruzzone R, White TW, Paul DL. Connections with connexins: the molecular basis of direct intercellular signaling. Eur J Biochem. May 15 1996;238(1):1-27. [Medline].

  45. Birouk N, Le Guern E, Maisonobe T, et al. X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiological study. Neurology. 1998;50:1074-82.

  46. Hahn AF, Bolton CF, White CM, Brown WF, Tuuha SE, Tan CC. Genotype/phenotype correlations in X-linked dominant Charcot-Marie-Tooth disease. Ann N Y Acad Sci. Sep 14 1999;883:366-82. [Medline].

  47. Dubourg O, Tardieu S, Birouk N, Gouider R, Léger JM, Maisonobe T. Clinical, electrophysiological and molecular genetic characteristics of 93 patients with X-linked Charcot-Marie-Tooth disease. Brain. Oct 2001;124(Pt 10):1958-67. [Medline].

  48. Züchner S, Mersiyanova IV, Muglia M, Bissar-Tadmouri N, Rochelle J, Dadali EL, et al. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. May 2004;36(5):449-51. [Medline].

  49. Koshiba T, Detmer SA, Kaiser JT, Chen H, McCaffery JM, Chan DC. Structural basis of mitochondrial tethering by mitofusin complexes. Science. Aug 6 2004;305(5685):858-62. [Medline].

  50. Baloh RH, Schmidt RE, Pestronk A, Milbrandt J. Altered axonal mitochondrial transport in the pathogenesis of Charcot-Marie-Tooth disease from mitofusin 2 mutations. J Neurosci. Jan 10 2007;27(2):422-30. [Medline].

  51. Emery AE. Population frequencies of inherited neuromuscular diseases--a world survey. Neuromuscul Disord. 1991;1(1):19-29. [Medline].

  52. Kurihara S, Adachi Y, Wada K, Awaki E, Harada H, Nakashima K. An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan. Neuroepidemiology. Sep-Oct 2002;21(5):246-50. [Medline].

  53. Ionasescu V, Searby C, Sheffield VC, Roklina T, Nishimura D, Ionasescu R. Autosomal dominant Charcot-Marie-Tooth axonal neuropathy mapped on chromosome 7p (CMT2D). Hum Mol Genet. Sep 1996;5(9):1373-5. [Medline].

  54. Nelis E, Van Broeckhoven C, De Jonghe P, Löfgren A, Vandenberghe A, Latour P. Estimation of the mutation frequencies in Charcot-Marie-Tooth disease type 1 and hereditary neuropathy with liability to pressure palsies: a European collaborative study. Eur J Hum Genet. 1996;4(1):25-33. [Medline].

  55. Lawson VH, Graham BV, Flanigan KM. Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene. Neurology. Jul 26 2005;65(2):197-204. [Medline].

  56. Garcia CA, Malamut RE, England JD, Parry GS, Liu P, Lupski JR. Clinical variability in two pairs of identical twins with the Charcot-Marie-Tooth disease type 1A duplication. Neurology. Nov 1995;45(11):2090-3. [Medline].

  57. Marques W Jr, Hanna MG, Marques SR, Sweeney MG, Thomas PK, Wood NW. Phenotypic variation of a new P0 mutation in genetically identical twins. J Neurol. Jul 1999;246(7):596-9. [Medline].

  58. Pfeiffer G, Wicklein EM, Ratusinski T, Schmitt L, Kunze K. Disability and quality of life in Charcot-Marie-Tooth disease type 1. J Neurol Neurosurg Psychiatry. Apr 2001;70(4):548-50. [Medline].

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

  60. Killian JM, Tiwari PS, Jacobson S, Jackson RD, Lupski JR. Longitudinal studies of the duplication form of Charcot-Marie-Tooth polyneuropathy. Muscle Nerve. Jan 1996;19(1):74-8. [Medline].

  61. Teunissen LL, Notermans NC, Franssen H, Van Engelen BG, Baas F, Wokke JH. Disease course of Charcot-Marie-Tooth disease type 2: a 5-year follow-up study. Arch Neurol. Jun 2003;60(6):823-8. [Medline].

  62. Thomas FP, Geller TJ, Hahn AF, et al. Modification of CMT1A phenotypes by independent co-existing neurogenetic disorders, McArdle disease and chromosome 5p trisomy. Ann NY Acad Sci. 1999;883:472-6.

  63. Thomas PK, Marques W Jr, Davis MB, Sweeney MG, King RH, Bradley JL, et al. The phenotypic manifestations of chromosome 17p11.2 duplication. Brain. Mar 1997;120 ( Pt 3):465-78. [Medline].

  64. Harding AE, Thomas PK. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain. Jun 1980;103(2):259-80. [Medline].

  65. Harding AE, Thomas PK. Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet. Oct 1980;17(5):329-36. [Medline].

  66. Rosen SA, Wang H, Cornblath DR, Uematsu S, Hurko O. Compression syndromes due to hypertrophic nerve roots in hereditary motor sensory neuropathy type I. Neurology. Sep 1989;39(9):1173-7. [Medline].

  67. Bienfait HM, Baas F, Koelman JH, de Haan RJ, van Engelen BG, Gabreëls-Festen AA. Phenotype of Charcot-Marie-Tooth disease Type 2. Neurology. May 15 2007;68(20):1658-67. [Medline].

  68. Hoogendijk J. E., Hensels G. W., Gabrëels-Festen A. A., et al. De novo mutation in hereditary motor and sensory neuropathy type 1. Lancet. 1992;339:1081-2.

  69. Berciano J, Garcia A, and Combarros O. Initial semiology in children with Charcot-Marie-Tooth disease 1A duplication. Muscle Nerve. 2003;27:34–39.

  70. Bienfait HM, Verhamme C, van Schaik IN, et al. Comparison of CMT1A and CMT2: similarities and differences. J Neurology. 2006;253:1572-80.

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

  72. Dyck PJ, Litchy WJ, Minnerath S, et al. Hereditary motor and sensory neuropathywith diaphragm and vocal cord paresis. Ann Neurol. 1994;35:608-15.

  73. De Jonghe P, Timmerman V, Ceuterick C, et al. The Thr124Met mutation in the peripheral myelin protein zero (MPZ) gene is associated with a clinically distinct Charcot–Marie–Tooth phenotype. Brain. 1999;122:281–290.

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

  75. Mastaglia FL, Nowak KJ, Stell R, Phillips BA, Edmondston JE, Dorosz SM, et al. Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry. Aug 1999;67(2):174-9. [Medline].

  76. De Jonghe P, Mersivanova I, Nelis E, Del Favero J, Martin JJ, Van Broeckhoven C, et al. Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann Neurol. Feb 2001;49(2):245-9. [Medline].

  77. Senderek J, Bergmann C, Ramaekers VT, Nelis E, Bernert G, Makowski A. Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy. Brain. Mar 2003;126(Pt 3):642-9. [Medline].

  78. Jordanova A, Irobi J, Thomas FP, Van Dijck P, Meerschaert K, Dewil M. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nat Genet. Feb 2006;38(2):197-202. [Medline].

  79. Bennett CL, Lawson VH, Brickell KL, Isaacs K, Seltzer W, Lipe HP. Late-onset hereditary axonal neuropathies. Neurology. Jul 1 2008;71(1):14-20. [Medline].

  80. Liao JP, Waclawik AJ. Nerve root hypertrophy in CMT type 1A. Neurology. Mar 9 2004;62(5):783. [Medline].

  81. Martinoli C, Schenone A, Bianchi S, Mandich P, Caponetto C, Abbruzzese M. Sonography of the median nerve in Charcot-Marie-Tooth disease. AJR Am J Roentgenol. Jun 2002;178(6):1553-6. [Medline].

  82. Dyck PJ, Lambert EH. Lower motor and primary sensory neuron diseases with peroneal muscular atrophy. II. Neurologic, genetic, and electrophysiologic findings in various neuronal degenerations. Arch Neurol. Jun 1968;18(6):619-25. [Medline].

  83. Lewis RA, Sumner AJ. The electrodiagnostic distinctions between chronic familial and acquired demyelinative neuropathies. Neurology. Jun 1982;32(6):592-6. [Medline].

  84. Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA. Uniform slowing of conduction velocities in Charcot-Marie-Tooth polyneuropathy type 1. Neurology. Dec 1993;43(12):2664-7. [Medline].

  85. Gabreëls-Festen A, Wetering RV. Human nerve pathology caused by different mutational mechanisms of the PMP22 gene. Ann N Y Acad Sci. Sep 14 1999;883:336-43. [Medline].

  86. Behse F, Buchthal F. Peroneal muscular atrophy (PMA) and related disorders. II. Histological findings in sural nerves. Brain. Mar 1977;100 Pt 1:67-85. [Medline].

  87. Donaghy M, Sisodiya SM, Kennett R, McDonald B, Haites N, Bell C. Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation. J Neurol Neurosurg Psychiatry. Dec 2000;69(6):799-805. [Medline].

  88. Watanabe M, Yamamoto N, Ohkoshi N, Nagata H, Kohno Y, Hayashi A. Corticosteroid- responsive asymmetric neuropathy with a myelin protein zero gene mutation. Neurology. Sep 10 2002;59(5):767-9. [Medline].

  89. Ginsberg L, Malik O, Kenton AR, Sharp D, Muddle JR, Davis MB. Coexistent hereditary and inflammatory neuropathy. Brain. Jan 2004;127(Pt 1):193-202. [Medline].

  90. Kaya F, Belin S, Bourgeois P, Micaleff J, Blin O, Fontés M. Ascorbic acid inhibits PMP22 expression by reducing cAMP levels. Neuromuscul Disord. Mar 2007;17(3):248-53. [Medline].

  91. Pareyson D, Schenone A, Fabrizi GM, Santoro L, Padua L, Quattrone A. A multicenter, randomized, double-blind, placebo-controlled trial of long-term ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL): the study protocol [EudraCT no.: 2006-000032-27]. Pharmacol Res. Dec 2006;54(6):436-41. [Medline].

  92. 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. Jan 2007;61(1):61-72. [Medline].

  93. Shy ME, Chen L, Swan ER, Taube R, Krajewski KM, Herrmann D, et al. Neuropathy progression in Charcot-Marie-Tooth disease type 1A. Neurology. Jan 29 2008;70(5):378-83. [Medline].

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

  95. Antognini JF. Anaesthesia for Charcot-Marie-Tooth disease: a review of 86 cases. Can J Anaesth. Apr 1992;39(4):398-400. [Medline].

[ CLOSE WINDOW ]

Further Reading

[ CLOSE WINDOW ]

Keywords

Charcot-Marie-Tooth neuropathy, Charcot-Marie-Tooth disorder, Charcot-Marie-Tooth syndrome, CMT, Hereditary Motor and Sensory Neuropathy, HMSN, peroneal muscular atrophy, Dejerine-Sottas syndrome

[ CLOSE WINDOW ]

Contributor Information and Disclosures

Author

Timothy C Parsons, MD, Fellow in EMG and Neuromuscular Disease, Department of Neurology, Columbia University Medical Center, New York
Timothy C Parsons, MD is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Thomas H Brannagan III, MD, Associate Professor of Clinical Neurology and Director, Peripheral Neuropathy Center, Columbia University, College of Physicians and Surgeons; Co-Director, EMG Laboratory, New York-Presbyterian Hospital, Columbia Campus, New York
Thomas H Brannagan III, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Peripheral Nerve Society
Disclosure: Nothing to disclose.

Medical Editor

Dianna Quan, MD, Associate Professor of Neurology, Director, Electromyography Laboratory, University of Colorado Health Sciences Center
Dianna Quan, MD is a member of the following medical societies: American Academy of Neurology, American Association of Neuromuscular and Electrodiagnostic Medicine, and Phi Beta Kappa
Disclosure: e-medicine Honoraria Other

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Neil A Busis, MD, Chief, Division of Neurology, Department of Medicine, Head, Clinical Neurophysiology Laboratory, University of Pittsburgh Medical Center-Shadyside
Neil A Busis, MD is a member of the following medical societies: American Academy of Neurology and American Association of Neuromuscular and Electrodiagnostic Medicine
Disclosure: Nothing to disclose.

CME Editor

Selim R Benbadis, MD, Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, University of South Florida School of Medicine, Tampa General Hospital
Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, and American Medical Association
Disclosure: Nothing to disclose.

Chief Editor

Nicholas Lorenzo, MD, Chief Editor, eMedicine Neurology; Consulting Staff, Neurology Specialists and Consultants
Nicholas Lorenzo, MD is a member of the following medical societies: Alpha Omega Alpha and American Academy of Neurology
Disclosure: Nothing to disclose.

 
 
HONcode

We subscribe to the
HONcode principles of the
Health On the Net Foundation

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

DISCLAIMER: The content of this Website is not influenced by sponsors. The site is designed primarily for use by qualified physicians and other medical professionals. The information contained herein should NOT be used as a substitute for the advice of an appropriately qualified and licensed physician or other health care provider. The information provided here is for educational and informational purposes only. In no way should it be considered as offering medical advice. Please check with a physician if you suspect you are ill.