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Neuromuscular Disorders in Clinical Practice pp 519–547Cite as

Charcot-Marie-Tooth Diseases

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Abstract

Charcot-Marie-Tooth (CMT) disease (also called hereditary motor and sensory neuropathy; HMSN) is a common disorder of children and adults, with autosomal-dominant, autosomal-recessive, and X-linked modes of inheritance. This chapter discusses the common CMT subtypes in detail, including CMT1A, CMTX, CMT1B, CMT2, and hereditary neuropathy with liability to pressure palsy. Other rare mutations, hereditary motor neuropathies, hereditary sensory and autonomic neuropathies, hereditary sensory neuropathies, and neuropathies with multiorgan disturbance, prominent central nervous system involvement, or specific metabolic dysfunction are reviewed briefly.

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References

  1. Hughes JT, Brownell B. Pathology of peroneal muscular atrophy (Charcot-Marie-Tooth Disease). J Neurol Neurosurg Psychiatry. 1972;35:648–57.

    Article  PubMed  CAS  Google Scholar 

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

    Google Scholar 

  3. Charcot JM. Sur une forme particulaire d’atrophie musculaire progressive souvent familial debutant par les pieds et les jambes et atteignant plus tard les mains. Rev Med. 1886;6:97–138.

    Google Scholar 

  4. Marie P. Forme spéciale de névrite interstitielle hypertrophique progressive de l’enfance. Rev Neurol (Paris). 1906;14:557–60.

    Google Scholar 

  5. Herringham WP. Muscular atrophy of the peroneal type affecting many members of a family. Brain. 1889;11:230–6.

    Article  Google Scholar 

  6. Dejerine H, Sottas J. Sur la névrite interstitielle, hypertrophique et progressive de l’enfance. CR Soc Biol (Paris). 1893;45:63–96.

    Google Scholar 

  7. Roussy G, Levy G. A sept cas d’une maladie familiale particulaire. Rev Neurol. 1926;33:427–50.

    Google Scholar 

  8. Allan W. Relation of hereditary pattern to clinical severity as illustrated by peroneal atrophy. Arch Intern Med. 1939;63:1123–31.

    Article  Google Scholar 

  9. 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. 1968;18:603–18.

    Article  PubMed  CAS  Google Scholar 

  10. Buchthal F, Behse F. Peroneal muscular atrophy (PMA) and related disorders. I. Clinical manifestations as related to biopsy findings. Brain. 1977;100:41–66.

    Article  PubMed  Google Scholar 

  11. Thomas PK, Calne DB. Motor nerve conduction velocity in ­peroneal muscular atrophy: evidence for genetic heterogeneity. J Neurol Neurosurg Psychiatry. 1974;37:68–75.

    Article  PubMed  CAS  Google Scholar 

  12. Harding AE, Thomas PK. Genetic aspects of hereditary motor and sensory neuropathy (types I and II). J Med Genet. 1980;176:329–36.

    Article  Google Scholar 

  13. Harding AE, Thomas PK. The clinical features of hereditary motor and sensory neuropathy types I and II. Brain. 1980;103:259–80.

    Article  PubMed  CAS  Google Scholar 

  14. Lewis RA, Sumner AJ. The electrodiagnostic distinctions between chronic familial and acquired demyelinating neuropathies. Neurology. 1982;32:592–6.

    Article  PubMed  CAS  Google Scholar 

  15. Kaku DA, Parry GJ, Malamut R, Lupski JR, Garcia CA. Uniform slowing of conduction velocities in Charcot-Marie-Tooth disease polyneuropathy type 1. Neurology. 1993;434:2664–7.

    Article  Google Scholar 

  16. Bradley W, Madrid R, Davis CJ. The peroneal muscular atrophy syndrome. Clinical genetic, electrophysiological and nerve biopsy studies. Part 3. Clinical, electrophysiological and pathological correlations. J Neurol Sci. 1977;32:123–36.

    Article  PubMed  CAS  Google Scholar 

  17. Madrid R, Bradley WG, Davis CJ. The peroneal muscular atrophy syndrome. Part 2. Observations on pathological changes in sural nerve biopsies. J Neurol Sci. 1977;32:91–122.

    Article  PubMed  CAS  Google Scholar 

  18. Davis CJ, Bradley W, Madrid R. The peroneal muscular atrophy syndrome. Clinical, genetic, electrophysiological and nerve biopsy studies. J Genet Hum. 1978;26:311–49.

    PubMed  CAS  Google Scholar 

  19. De Jonghe P, Timmerman V, Nelis E, et al. Charcot-Marie-Tooth disease and related peripheral neuropathies. J Peripher Nerv Syst. 1997;2:370–87.

    PubMed  Google Scholar 

  20. 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. 1982;34:388–94.

    PubMed  CAS  Google Scholar 

  21. Raeymaekers P, De Jonghe P, Backhovens H, et al. Absence of genetic linkage of Charcot-Marie-Tooth disease (HMSN Ia) with chromosome 1 gene markers. Neurology. 1989;39:844–6.

    Article  PubMed  CAS  Google Scholar 

  22. Middleton-Price HR, Harding AE, Monteiro C, Berciano J, Malcolm S. Linkage of hereditary motor and sensory neuropathy type Ito the pericentromeric region of chromosome 17. Am J Hum Genet. 1990;46:92–4.

    PubMed  CAS  Google Scholar 

  23. Vance JM, Nicholson GA, Yamaoka LH, et al. Linkage of Charcot-Marie-Tooth neuropathy type 1a to chromosome 17. Exp Neurol. 1989;104:186–9.

    Article  PubMed  CAS  Google Scholar 

  24. Lupski JR, de Oca-Luna RM, Slaugenhaupt S. DNA duplication associated with Charcot-Marie-Tooth disease type 1A. Cell. 1991;66:219–32.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  26. Suter U, Moskow JJ, Welcher AA, et al. A leucine-to-proline mutation in the putative first transmembrane domain of the 22-kDa peripheral myelin protein in the trembler-J mouse. Proc Natl Acad Sci U S A. 1992;89:4382–6.

    Article  PubMed  CAS  Google Scholar 

  27. Suter U, Welcher AA, Ozcelik T, et al. Trembler mouse carries a point mutation in a myelin gene. Nature. 1992;356:241–4.

    Article  PubMed  CAS  Google Scholar 

  28. 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.

    Article  PubMed  CAS  Google Scholar 

  29. Valentijn LJ, Baas F, Wolterman RA, et al. Identical point mutations of peripheral myelin protein 22 kD in Trembler-J mouse and Charcot-Marie-Tooth disease type-1A. Nat Genet. 1992;2:288–91.

    Article  PubMed  CAS  Google Scholar 

  30. Nelis E, Timmerman V, De Jonghe P, et al. Rapid screening of myelin genes in CMT1 patients by SSCP analysis: identification of new mutations and polymorphisms in the protein zero gene. Hum Genet. 1994;94:653–7.

    Article  PubMed  CAS  Google Scholar 

  31. Magyar JP, Martini R, Ruelicke T, et al. Impaired differentiation of Schwann cells in transgenic mice with increased PMP22 gene dosage. J Neurosci. 1996;16:5351–60.

    PubMed  CAS  Google Scholar 

  32. Sereda M, Griffiths I, Puhlhofer A, et al. A transgenic rat model of Charcot-Marie-Tooth disease. Neuron. 1996;16:1049–60.

    Article  PubMed  CAS  Google Scholar 

  33. Huxley C, Passage E, Manson A, et al. Construction of a mouse model of Charcot-Marie-Tooth disease type 1A by pronuclear injection of human YAC DNA. Hum Mol Genet. 1996;5:563–9.

    Article  PubMed  CAS  Google Scholar 

  34. 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.

    Article  PubMed  CAS  Google Scholar 

  35. Stankiewicz P, Parka SS, Holder SE, et al. Trisomy 17p10-p12 resulting from a supernumerary marker chromosome derived from chromosome 17: molecular analysis and delineation of the phenotype. Clin Genet. 2001;60:336–44.

    Article  PubMed  CAS  Google Scholar 

  36. Bergoffen J, Scherer SS, Wang S. Connexin mutations in X-linked Charcot-Marie-Tooth disease. Science. 1993;262:2039–42.

    Article  PubMed  CAS  Google Scholar 

  37. Kennerson ML, Yiu EM, Chuang DT, et al. A new locus for X-linked dominant Charcot–Marie–Tooth disease (CMTX6) is caused by mutations in the pyruvate dehydrogenase kinase isoenzyme 3 (PDK3) gene. Hum Mol Genet. 2013;22(7):1404–16.

    Article  PubMed  CAS  Google Scholar 

  38. Hayasaka K, Himoro M, Sawaishi Y, et al. De novo mutation of the myelin P0 gene in Dejerine-Sottas disease (hereditary motor and sensory neuropathy type III). Nat Genet. 1993;5:266–8.

    Article  PubMed  CAS  Google Scholar 

  39. Kulkens T, Bolhuis PA, Wolterman RA, et al. Deletion of the serine 34 codon from the major peripheral myelin protein P0 gene in Charcot-Marie-Tooth disease type 1B. Nat Genet. 1993;5:35–9.

    Article  PubMed  CAS  Google Scholar 

  40. Su Y, Brooks DG, Li L, et al. Myelin protein zero gene mutated in Charcot-Marie-Tooth disease type 1B patients. Proc Natl Acad Sci U S A. 1993;90:10856–60.

    Article  PubMed  CAS  Google Scholar 

  41. Warner LE, Mancias P, Butler IJ, et al. Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat Genet. 1998;18:382–4.

    Article  PubMed  CAS  Google Scholar 

  42. Chance PF, Alderson MK, Leppig KA, et al. DNA deletion associated with hereditary neuropathy with liability to pressure palsies. Cell. 1993;72:143–51.

    Article  PubMed  CAS  Google Scholar 

  43. Zhang F, Seeman P, Liu P, et al. Mechanisms for nonrecurrent genomic rearrangements associated with CMT1A or HNPP: rare CNVs as a cause for missing heritability. Am J Hum Genet. 2010;86:892–903.

    Article  PubMed  CAS  Google Scholar 

  44. Chance PF, Lensch MW, Lipe H, et al. Hereditary neuralgic amyotrophy and hereditary neuropathy with liability to pressure palsies: two distinct genetic disorders. Neurology. 1994;44:2253–7.

    Article  PubMed  CAS  Google Scholar 

  45. Pellegrino JE, George RA, Biegel J, et al. Hereditary neuralgic amyotrophy: evidence for genetic homogeneity and mapping to chromosome 17q25. Hum Genet. 1997;101:277–83.

    Article  PubMed  CAS  Google Scholar 

  46. Nelis E, Van Broeckhoven C, De Jonghe P, et al. 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;4:25–33.

    PubMed  CAS  Google Scholar 

  47. Warner LE, Hilz MJ, Appel SH. Clinical phenotypes of different MPZ (P0) mutations may include Charcot- Marie-Tooth type 1B, Dejerine-Sottas, and congenital hypomyelination. Neuron. 1996;17:451–60.

    Article  PubMed  CAS  Google Scholar 

  48. Reilly MM. Genetically determined neuropathies. J Neurol. 1998;245:6–13.

    Article  PubMed  CAS  Google Scholar 

  49. Inherited Peripheral Neuropathies Mutation Database at www.molgen.ua.ac.be/CMTMutations/

  50. D’Urso D, Erhardt P, Muller H. Peripheral myelin protein 22 and protein zero: a novel association in peripheral nervous system myelin. J Neurosci. 1999;19:3396–403.

    PubMed  Google Scholar 

  51. Friedman HC, Aguayo AJ, Bray GM. Trophic factors in neuron-Schwann cell interactions. Ann N Y Acad Sci. 1999;883:427–38.

    Article  PubMed  CAS  Google Scholar 

  52. Barbaria EM, Kohl B, Buhren BA, et al. The alpha-chemokine CXCL14 is up-regulated in the sciatic nerve of a mouse model of Charcot-Marie-Tooth disease type 1A and alters myelin gene expression in cultured Schwann cells. Neurobiol Dis. 2009;33:448–58.

    Article  PubMed  CAS  Google Scholar 

  53. Skre H. Genetic and clinical aspects of Charcot-Marie-Tooth’s disease. Clin Genet. 1974;6:98–118.

    Article  PubMed  CAS  Google Scholar 

  54. Emery AE. Population frequencies of inherited neuromuscular diseases: a world survey. Neuromuscul Disord. 1991;1:19–29.

    Article  PubMed  CAS  Google Scholar 

  55. Kurihara S, Adachi Y, Wada K. An epidemiological genetic study of Charcot-Marie-Tooth disease in Western Japan. Neuro­epidemiology. 2002;21:246–50.

    Article  PubMed  Google Scholar 

  56. 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;7:529–32.

    Article  PubMed  CAS  Google Scholar 

  57. Martin J-J, Brice A, Van Broeckhoven C. 4th Workshop of the European CMT-Consortium – 62nd ENMC international workshop: rare forms of Charcot-Marie-Tooth disease and related disorders. Neuromuscul Disord. 1999;9:279–87.

    Article  Google Scholar 

  58. Thomas PK, Marques Jr W, Davis MB. The phenotypic manifestations of chromosome 17p11.2 duplication. Brain. 1997;120:465–78.

    Article  PubMed  Google Scholar 

  59. Auer-Grumbach M, Strasser-Fuchs S, Wagner K, Korner E, Fazekas F. Roussy-Levy syndrome is a phenotypic variant of Charcot-Marie-Tooth syndrome IA associated with a duplication on chromosome 17p11.2. J Neurol Sci. 1998;154:72–5.

    Article  PubMed  CAS  Google Scholar 

  60. Plante-Bordeneuve V, Guiochon-Mantel A, Lacroix C. The Roussy-Levy family: from the original description to the gene. Ann Neurol. 1999;46:770–3.

    Article  PubMed  CAS  Google Scholar 

  61. Magnaghi V, Cavarretta I, Zucchi I, et al. P0 gene expression is modulated by androgens in the sciatic nerve of adult male rats. Mol Brain Res. 1999;70:36–44.

    Article  PubMed  CAS  Google Scholar 

  62. Melcangi RC, Magnaghi V, Cavarretta I, et al. Progesterone derivatives are able to influence peripheral myelin protein 22 and P0 gene expression: possible mechanisms of action. J Neurosci Res. 1999;56:349–57.

    Article  PubMed  CAS  Google Scholar 

  63. Amato A, Barohn R. Hereditary neuropathy with liability to pressure palsies: association with central nervous system demyelination. Muscle Nerve. 1996;19:770–3.

    Article  PubMed  CAS  Google Scholar 

  64. Tackenberg B, Moller JC, Rindock H, et al. CNS involvement in hereditary neuropathy with pressure palsies (HNPP). Neurology. 2006;67:2250–2.

    Article  PubMed  CAS  Google Scholar 

  65. Shaibani A, Gooch C, Harati Y. Moving toes and myoclonus associated with hereditary neuropathy with liability to pressure palsy (HNPP). Muscle Nerve. 1997;20:881–3.

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  Google Scholar 

  67. 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;122:281–90.

    Article  PubMed  Google Scholar 

  68. Blanquet-Grossard F, Pham-Dinh D, Dautigny A, et al. Charcot-Marie-Tooth type 1B neuropathy: a mutation at the single glycosylation site in the major peripheral myelin glycoprotein P0. Hum Mutat. 1996;8:185–6.

    Article  PubMed  CAS  Google Scholar 

  69. Bienfait HM, Baas F, Gabreels-Festen AA, et al. Two amino-acid substitutions in the myelin protein zero gene of a case of Charcot-Marie-Tooth disease associated with light-near dissociation. Neuromuscul Disord. 2002;12:281–5.

    Article  PubMed  CAS  Google Scholar 

  70. Stojkovic T, Seze J, Dubourg O, et al. Autonomic and respiratory dysfunction in Charcot-Marie-Tooth disease due to Thr124Met mutation in the myelin protein zero gene. Clin Neurophysiol. 2003;114:1609–14.

    Article  PubMed  CAS  Google Scholar 

  71. Marques Jr W, Sweeney MG, Wood NW, Wroe SJ, Marques W. Central nervous system involvement in a novel connexin 32 mutation affecting identical twins. J Neurol Neurosurg Psychiatry. 1999;66:803–4.

    Article  PubMed  Google Scholar 

  72. Panas M, Karadimas C, Avramopoulos D, Vassilopoulos D. Central nervous system involvement in four patients with Charcot-Marie-Tooth disease with connexin 32 extracellular mutations. J Neurol Neurosurg Psychiatry. 1998;65:947–8.

    Article  PubMed  CAS  Google Scholar 

  73. Hanemann CO, Bergmann C, Senderek J, Zerres K, Sperfeld A-D. Transient, recurrent, white matter lesions in X-linked Charcot-Marie-Tooth disease with novel connexin 32 mutation. Arch Neurol. 2003;60:605–9.

    Article  PubMed  Google Scholar 

  74. Kawakami H, Inoue K, Sakakihara I, Nakamura S. Novel mutation in X-linked Charcot-Marie-Tooth disease associated with CNS impairment. Neurology. 2002;59:923–6.

    Article  PubMed  CAS  Google Scholar 

  75. Siskind C, Feely SM, Bernes S, Shy ME, Garbern JY. Persistent CNS dysfunction in a boy with CMT1X. J Neurol Sci. 2009;279:109–13.

    Article  PubMed  Google Scholar 

  76. Aboussouan LS, Lewis RA, Shy ME. Disorders of pulmonary function, sleep, and the upper airway in Charcot-Marie-Tooth disease. Lung. 2007;185:1–7.

    Article  PubMed  Google Scholar 

  77. Boerkoel CF, Takashima H, Garcia CA, et al. Charcot-Marie-Tooth disease and related neuropathies: mutation distribution and genotype-phenotype correlation. Ann Neurol. 2002;51:190–201.

    Article  PubMed  CAS  Google Scholar 

  78. Huehne K, Benes V, Thiel C, et al. Novel mutations in the Charcot-Marie-Tooth disease genes PMP22, MPZ, and GJB1. Hum Mutat. 2003;21:100.

    Article  PubMed  CAS  Google Scholar 

  79. Joo IS, Ki CS, Joo SY, Huh K, Kim JW. A novel point mutation in PMP22 gene associated with a familial case of Charcot-Marie-Tooth disease type 1A with sensorineural deafness. Neuromuscul Disord. 2004;14:325–8.

    Article  PubMed  Google Scholar 

  80. Sambuughin N, de Bantel A, McWilliams S, Sivakumar K. Deafness and CMT disease associated with a novel four amino acid deletion in the PMP22 gene. Neurology. 2003;60:506–8.

    Article  PubMed  CAS  Google Scholar 

  81. Gabreels-Festen A, Gabreels FJ, Joosten EM, Vingerhoets HM, Renier WO. Hereditary neuropathy with liability to pressure palsies in childhood. Neuropediatrics. 1992;23:138–43.

    Article  PubMed  CAS  Google Scholar 

  82. Kilfoyle DH, Dyck PJ, Wu Y, et al. Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis. J Neurol Neurosurg Psychiatry. 2006;77:963–6.

    Article  PubMed  CAS  Google Scholar 

  83. Stojkovic T, Latour P, Vandenberghe A, Hurtevent JF, Vermersch P. Sensorineural deafness in X-linked Charcot-Marie-Tooth disease with connexin 32 mutation (R142Q). Neurology. 1999;52:1010–4.

    Article  PubMed  CAS  Google Scholar 

  84. Priest JM, Fischbeck KH, Nouri N, Keats BJB. A locus for axonal motor-sensory neuropathy with deafness and mental retardation maps to Xq24-q26. Genomics. 1995;29:409–12.

    Article  PubMed  CAS  Google Scholar 

  85. Kim HJ, Sohn KM, Shy ME, et al. Mutations in PRPS1, which encodes the phosphoribosyl pyrophosphate synthetase enzyme critical for nucleotide biosynthesis, cause hereditary peripheral neuropathy with hearing loss and optic neuropathy (CMTX5). Am J Hum Genet. 2007;81:552–8.

    Article  PubMed  CAS  Google Scholar 

  86. Thomas FP, Geller TJ, Hahn AF. Modification of CMT1 phenotypes by independent co-existing neurogenetic disorders, McArdle disease and chromosome 5p trisomy. Ann N Y Acad Sci. 1999;883:472–6.

    Article  PubMed  CAS  Google Scholar 

  87. Hisama FM. Familial periodic paralysis and Charcot-Marie-Tooth disease in a 7-generation family. Arch Neurol. 2005;62:135–8.

    Article  PubMed  Google Scholar 

  88. Pegoraro E, Gavassini BF, Benedetti S, et al. Co-segregation of LMNA and PMP22 gene mutations in the same family. Neuromuscul Disord. 2005;15:858–62.

    Article  PubMed  Google Scholar 

  89. Bhatt A, Farooq MU, Aburashed R, et al. Hereditary neuropathy with liability to pressure palsies and amyotrophic lateral sclerosis. Neurol Sci. 2009;30:241–5.

    Article  PubMed  Google Scholar 

  90. Marsh EA, Robinson DO. A case of rare recessive oculopharyngeal muscular dystrophy (OPMD) coexisting with hereditary neuropathy with liability to pressure palsies (HNPP). Clin Neurol Neurosurg. 2008;110:525–8.

    Article  PubMed  Google Scholar 

  91. Balestrini MR, Cavaletti G, D’Angelo A, Tredici G. Infantile hereditary neuropathy with hypomyelination: report of two siblings with different expressivity. Neuropediatrics. 1991;22:65–70.

    Article  PubMed  CAS  Google Scholar 

  92. 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. 2003;60:823–8.

    Article  PubMed  Google Scholar 

  93. Rudnik-Schoneborn S, Rohrig D, Nicholson G, Zerres K. Pregnancy and delivery in Charcot-Marie-Tooth disease type-1. Neurology. 1993;43:2011–6.

    Article  PubMed  CAS  Google Scholar 

  94. Gastaut JL, Benaim J, Livet MO, Philip N. Charcot Marie Tooth disease: exacerbation in pregnancy. Rev Neurologique. 2000;156:890–1.

    CAS  Google Scholar 

  95. Dematteis M, Pepin J, Jeanmart M, et al. Charcot-Marie-Tooth disease and sleep apnea syndrome: a family study. Lancet. 2001;357:267–72.

    Article  PubMed  CAS  Google Scholar 

  96. Pfeiffer G, Ratusinski T, Schmitt L, Kunze K. Disability and quality of life in Charcot-Marie-Tooth disease type 1. J Neurol Neurosurg Psychiatry. 2001;70:548–50.

    Article  PubMed  CAS  Google Scholar 

  97. Pareyson D, Testa D, Morbin M, et al. Does CMT1A homozygosity cause more severe disease with root hypertrophy and higher CSF proteins? Neurology. 2003;60(10):1721–2.

    Article  PubMed  CAS  Google Scholar 

  98. Le Forestier N, LeGuern E, Coullin P, et al. Recurrent polyradiculoneuropathy with the 17p11.2 deletion. Muscle Nerve. 1997;20(9):1184–6.

    Article  PubMed  Google Scholar 

  99. Hattori N, Yamamoto M, Yoshihara T, et al. 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. 2003;126:134–51.

    Article  PubMed  Google Scholar 

  100. Fabrizi GM, Ferrarini M, Cavallaro T, Jarre L, Polo A, Rizzuto N. A somatic and germline mosaic mutation in MPZ/P(0) mimics recessive inheritance of CMT1B. Neurology. 2001;57:101–5.

    Article  PubMed  CAS  Google Scholar 

  101. Beckmann A, Schroder JM. Screening for Charcot-Marie-Tooth type 1A and hereditary neuropathy with liability to pressure palsy in archival nerve biopsy samples by direct-double-differential PCR. Acta Neuropathol (Berlin). 2000;100:459–63.

    Article  CAS  Google Scholar 

  102. Krajewski K, Lewis RA, Fuerst DR, et al. Neurological dysfunction and axonal degeneration in Charcot-Marie-Tooth disease type 1A. Brain. 2000;123:1516–27.

    Article  PubMed  Google Scholar 

  103. Hoogendijk JE, De Visser M, Bolhuis PA, Hart AA, Ongerboer de Visser BW. Hereditary motor and sensory neuropathy type I: clinical and neurographical features of the 17P duplication subtype. Muscle Nerve. 1994;17:85–90.

    Article  PubMed  CAS  Google Scholar 

  104. Yiu EM, Burns J, Ryan MM, Ouvrier RA. Neurophysiologic abnormalities in children with Charcot-Marie-Tooth disease type 1A. J Peripher Nerv Syst. 2008;13:236–41.

    Article  PubMed  Google Scholar 

  105. Nodera H, Bostock H, Kuwabara S, et al. Nerve excitability properties in Charcot-Marie-Tooth disease type 1A. Brain. 2004;127(Pt 1):203–11.

    Article  PubMed  Google Scholar 

  106. Norreel JC, Vinay L, Fontes M, Clarac F. Close relationship between motor impairments and loss of functional motoneurons in a Charcot-Marie-Tooth type 1A model. Neuroscience. 2003;116:695–703.

    Article  PubMed  CAS  Google Scholar 

  107. Gabreels-Festen A, Joosten EM, Gabreels FG, et al. Early morphological features in dominantly inherited demyelinating motor and sensory neuropathy (HMSN type I). J Neurol Sci. 1992;107:145–54.

    Article  PubMed  CAS  Google Scholar 

  108. Mastaglia FL, Nowak KJ, Stell R, et al. Novel mutation in the myelin protein zero gene in a family with intermediate hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry. 1999;67:174–9.

    Article  PubMed  CAS  Google Scholar 

  109. Andersson PB, Yuen E, Parko K, So YT. Electrodiagnostic features of hereditary neuropathy with liability to pressure palsies. Neurology. 2000;54:40–4.

    Article  PubMed  CAS  Google Scholar 

  110. Li J, Krajewski K, Shy ME, Lewis RA. Hereditary neuropathy with liability to pressure palsy: the electrophysiology fits the name. Neurology. 2002;58:1769–73.

    Article  PubMed  Google Scholar 

  111. Mouton P, Tardieu S, Gouider R, et al. Spectrum of clinical and eletrophysiologic features in HNPP patients with the 17p11.2 deletion. Neurology. 1999;52:1440–6.

    Article  PubMed  CAS  Google Scholar 

  112. Infante J, Garcia A, Combarros O, et al. Diagnostic strategy for familial and sporadic cases of neuropathy associated with 17p11.2 deletion. Muscle Nerve. 2001;24:1149–55.

    Article  PubMed  CAS  Google Scholar 

  113. Gouider RL, Gugenheim M, Tardieu S, et al. Clinical, electrophysiologic, and molecular correlations in 13 families with hereditary neuropathy with liability to pressure palsies and a chromosome 17p11.2 deletion. Neurology. 1995;45:2018–23.

    Article  PubMed  CAS  Google Scholar 

  114. Liao JP, Waclawik AJ. Nerve root hypertrophy in CMT type 1A. Neurology. 2004;62:783.

    Article  PubMed  Google Scholar 

  115. Gallardo E, Garcia A, Combarros O, Berciano J. Charcot-Marie-Tooth disease type 1A duplication: spectrum of clinical and magnetic resonance imaging features in leg and foot muscles. Brain. 2006;129:426–37.

    Article  PubMed  Google Scholar 

  116. Chung KW, Suh BC, Shy ME, et al. Different clinical and magnetic resonance imaging features between Charcot-Marie-Tooth disease type 1A and 2A. Neuromuscul Disord. 2008;18:610–8.

    Article  PubMed  CAS  Google Scholar 

  117. Gallardo E, Claeys KG, Nelis E, et al. Magnetic resonance imaging findings of leg musculature in Charcot-Marie-Tooth disease type 2 due to dynamin 2 mutation. J Neurol. 2008;255:986–92.

    Article  PubMed  CAS  Google Scholar 

  118. Cartwright MS, Brown ME, Eulitt P, Walker FO, Lawson VH, Caress JB. Diagnostic nerve ultrasound in Charcot-Marie-Tooth disease type 1B. Muscle Nerve. 2009;40:98–102.

    Article  PubMed  Google Scholar 

  119. Chung KW, Kim SB, Park KD, et al. Early onset severe and late-onset mild Charcot-Marie-Tooth disease with mitofusin 2 (MFN2) mutations. Brain. 2006;129:2103–18.

    Article  PubMed  CAS  Google Scholar 

  120. Lopes J, Ravise N, Vandenberghe A, et al. Fine mapping of de novo CMT1A and HNPP rearrangements within CMT1A-REPs evidences two distinct sex-dependent mechanisms and candidate sequences involved in recombination. Hum Mol Genet. 1998;7:141–8.

    Article  PubMed  CAS  Google Scholar 

  121. Burns J, Bray P, Cross LA, North KN, Ryan MM, Ouvrier RA. Hand involvement in children with Charcot-Marie-Tooth disease type 1A. Neuromuscul Disord. 2008;18:970–3.

    Article  PubMed  Google Scholar 

  122. Munch C, Epplen JT, Meins M, Meyer R, Weber JR, Meyer T. Severe Guillain-Barré syndrome associated with chromosome 17p11.2-12 duplication. Muscle Nerve. 2008;37:256–8.

    Article  PubMed  Google Scholar 

  123. Auer-Grumbach M, Wagner K, Strasser-Fuchs S. Clinical predominance of proximal upper limb weakness in CMT1A syndrome. Muscle Nerve. 2000;23:1243–9.

    Article  PubMed  CAS  Google Scholar 

  124. Murakami T, Oomori H, Hara A, et al. Atypical phenotype of Charcot-Marie-Tooth disease type 1A. Muscle Nerve. 1999;22:1593–6.

    Article  PubMed  CAS  Google Scholar 

  125. Abe KT, Lino AM, Hirata MT, et al. A novel stop codon mutation in the PMP22 gene associated with a variable phenotype. Neuromuscul Disord. 2004;14:313–20.

    Article  PubMed  CAS  Google Scholar 

  126. Fusco C, Frattini D, Scarano A, Giustina ED. Congenital pes cavus in a Charcot-Marie-tooth disease type 1A newborn. Pediatr Neurol. 2009;40:461–4.

    Article  PubMed  Google Scholar 

  127. Vital A, Vital C, Lagueny A, et al. Inflammatory demyelination in a patient with CMT1A. Muscle Nerve. 2003;28:373–6.

    Article  PubMed  Google Scholar 

  128. Ginsberg L, Malik O, Kenton AR, et al. Coexistent hereditary and inflammatory neuropathy. Brain. 2004;127:193–202.

    Article  PubMed  Google Scholar 

  129. Desurkar A, Link JP, Mills K, et al. Charcot-Marie-Tooth (CMT) disease 1A with superimposed inflammatory polyneuropathy in children. Neuropediatrics. 2009;40:85–8.

    Article  PubMed  CAS  Google Scholar 

  130. Losito L, De Rinaldis M, Gennaro L, et al. Charcot-Marie-Tooth type 1a in a child with Long QT syndrome. Eur J Paediatr Neurol. 2009;13:459–62.

    Article  PubMed  Google Scholar 

  131. Yoshikawa H, Nishimura T, Nakatsuji Y, et al. Elevated expression of messenger RNA for peripheral myelin protein 22 in biopsied peripheral nerves of patients with Charcot-Marie-Tooth disease type 1A. Ann Neurol. 1994;35:445–50.

    Article  PubMed  CAS  Google Scholar 

  132. Müller HW. New vistas on the pathomechanism of Charcot-Marie-Tooth and related peripheral neuropathies. Ann N Y Acad Sci. 1999;883:152–9.

    Article  PubMed  Google Scholar 

  133. Massa R, Palumbo C, Cavallaro T, et al. Overexpression of ErbB2 and ErbB3 receptors in Schwann cells of patients with Charcot-Marie-Tooth disease type 1A. Muscle Nerve. 2006;33:342–9.

    Article  PubMed  CAS  Google Scholar 

  134. Tobler AR, Notterpek L, Naef R, et al. Transport of Trembler-J mutant peripheral myelin protein 22 is blocked in the intermediate compartment and affects the transport of the wild-type protein by direct interaction. J Neurosci. 1999;19:2027–36.

    PubMed  CAS  Google Scholar 

  135. Adlkofer K, Naef R, Suter U. Analysis of compound heterozygous mice reveals that the Trembler mutation can behave as a gain-of-function allele. J Neurosci Res. 1997;49:671–80.

    Article  PubMed  CAS  Google Scholar 

  136. Garbay B, Domec C, Fournier M, Bonnet J. Developmental expression of the protein zero glycoprotein and basic protein mRNAs in normal and trembler mutant mice. J Neurochem. 1989;53:907–11.

    Article  PubMed  CAS  Google Scholar 

  137. Vallat JM, Sindou P, Preux PM, et al. Ultrastructural PMP22 expression in inherited demyelinating neuropathies. Ann Neurol. 1996;39:813–7.

    Article  PubMed  CAS  Google Scholar 

  138. Taioli F, Cabrini I, Cavallaro T, Acler M, Fabrizi GM. Inherited demyelinating neuropathies with micromutations of peripheral myelin protein 22 gene. Brain. 2011;134:608–17.

    Article  PubMed  Google Scholar 

  139. Li J, Bai Y, Ghandour K, et al. Skin biopsies in myelin-related neuropathies: bringing molecular pathology to the bedside. Brain. 2005;128:1168–77.

    Article  PubMed  Google Scholar 

  140. Tyson J, Malcom S, Thomas PK, Harding AE. Deletions of chromosome 17p11.2 in multifocal neuropathies. Ann Neurol. 1996;39:180–6.

    Article  PubMed  CAS  Google Scholar 

  141. Lonnqvist T, Pihko H. Hereditary neuropathy with liability to pressure palsies (HNPP) in a toddler presenting with toe-walking, pain and stiffness. Neuromuscular Dis. 2003;13:827–9.

    Article  Google Scholar 

  142. Saporta AS, Sottile SL, Miller LJ, Feely SME, Siskind CE, Shy ME. Charcot-Marie-Tooth disease subtypes and genetic testing strategies. Ann Neurol. 2011;69:22–33.

    Article  PubMed  Google Scholar 

  143. Rao CV, Diamond AL, Thomas FP. Greater occipital nerve involvement in hereditary neuropathy with liability to pressure palsy (HNPP). Ann Neurol. 2004;56:S61.

    Article  CAS  Google Scholar 

  144. Li J, Krajewski K, Lewis RA, Shy ME. Loss-of-function phenotype of hereditary neuropathy with liability to pressure palsies. Muscle Nerve. 2004;29:205–10.

    Article  PubMed  Google Scholar 

  145. Del Colle R, Fabrizi GM, Turazzini M, Cavallaro T, Silvestri M, Rizzuto N. Hereditary neuropathy with liability to pressure palsies: electrophysiological and genetic study of a family with carpal tunnel syndrome as only clinical manifestation. Neurol Sci. 2003;24:57–60.

    PubMed  Google Scholar 

  146. Simonetti S. Lesion of the anterior branch of axillary nerve in a patient with hereditary neuropathy with liability to pressure palsies. Eur J Neurol. 2000;7:577–9.

    Article  PubMed  CAS  Google Scholar 

  147. Orstavik K, Skard Heier M, Young P, Stögbauer F. Brachial plexus involvement as the only expression of hereditary neuropathy with liability to pressure palsies. Muscle Nerve. 2001;24:1093–6.

    Article  PubMed  CAS  Google Scholar 

  148. Bosch E, Chui H, Martin M, Cancilla PA. Brachial plexus involvement in familial pressure-sensitive neuropathy: eletrophysiological and morphological findings. Ann Neurol. 1980;8:620–4.

    Article  PubMed  CAS  Google Scholar 

  149. Martinelli P, Fabbri R, Moretto G, Gabellini AS, D’Alessandro R, Rizzuto N. Recurrent familial brachial plexus palsies as the only clinical expression of ‘tomaculous’ neuropathy. Eur Neurol. 1989;29:61–6.

    Article  PubMed  CAS  Google Scholar 

  150. Stogbauer F, Young P, Kerschensteiner M, Ringelstein EB, Assmann G, Funke H. Recurrent brachial plexus palsies as the only clinical expression of hereditary neuropathy with liability to pressure palsies associated with a de novo deletion of the peripheral myelin protein-22 gene. Muscle Nerve. 1998;21(9):1199–201.

    Article  PubMed  CAS  Google Scholar 

  151. Kumar N, Cole J, Parry G. Variability of presentation in hereditary neuropathy with liability to pressure palsy results in underrecognition. Ann N Y Acad Sci. 1999;883:344–50.

    Article  PubMed  CAS  Google Scholar 

  152. Pareyson D, Scaioli V, Taroni F, et al. Phenotypic heterogeneity in hereditary neuropathy with liability to pressure palsies associated with chromosome 17p11.2-12 deletion. Neurology. 1996;46:1133–7.

    Article  PubMed  CAS  Google Scholar 

  153. Pareyson D, Solari A, Taroni F, et al. Detection of hereditary neuropathy with liability to pressure palsies among patients with acute painless mononeuropathy or plexopathy. Muscle Nerve. 1998;21:1686–91.

    Article  PubMed  CAS  Google Scholar 

  154. Barisic N, Skarpa D, Jusic A, Jadro-Santel D. Steroid responsive familial neuropathy with liability to pressure palsies. Neuropediatrics. 1990;21:191–2.

    Article  PubMed  CAS  Google Scholar 

  155. Joy J, Oh S. Tomaculous neuropathy presenting as acute recurrent polyneuropathy. Ann Neurol. 1989;26:98–100.

    Article  PubMed  CAS  Google Scholar 

  156. Crum B, Sorenson E, Abad G, Dyck PJ. Fulminant case of hereditary neuropathy with liability to pressure palsy. Muscle Nerve. 2000;23:979–83.

    Article  PubMed  CAS  Google Scholar 

  157. Lynch JM, Hennessy M. HNPP presenting as sciatic neuropathy. J Peripher Nerv Syst. 2005;10:1–2.

    Article  PubMed  Google Scholar 

  158. Heckmann JG, Dutsch M, Buslei R. Hereditary neuropathy with liability to pressure palsy combined with schwannomas of the median and medial plantar nerves. Muscle Nerve. 2007;35:122–4.

    Article  PubMed  Google Scholar 

  159. Nicholson G, Valentijn L, Cherryson A, et al. A frame shift mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies. Nat Genet. 1994;6:263–6.

    Article  PubMed  CAS  Google Scholar 

  160. Taroni F, Botti S, Sghirlanzoni A, et al. A nonsense mutation in the PMP22 gene in hereditary neuropathy with liability to pressure palsies (HNPP) not associated with the 17p11.2 deletion. Am J Hum Genet. 1995;57:229.

    Google Scholar 

  161. Taroni F, Botti S, Sghirlanzoni A, Pareyson D. PMP22 and MPZ point mutations in Italian families with hereditary neuropathy with liability to pressure palsies (HNPP) and Dejerine-Sottas disease (DSD). Am J Hum Genet. 1996;59:A288.

    Google Scholar 

  162. Meuleman J, Pou-Serradell A, Lofgren A, et al. A novel 3’-splice site mutation in peripheral myelin protein 22 causing hereditary neuropathy with liability to pressure palsies. Neuromuscul Disord. 2001;11:400–3.

    Article  PubMed  CAS  Google Scholar 

  163. Maycox PR, Ortuno D, Burrola P, et al. A transgenic mouse model for human hereditary neuropathy with liability for human hereditary neuropathy with liability to pressure palsies. Mol Cell Neurosci. 1997;8:405–16.

    Article  PubMed  CAS  Google Scholar 

  164. Suter U, Nave K. Transgenic mouse models of CMT1A and HNPP. Ann N Y Acad Sci. 1999;883:247–53.

    Article  PubMed  CAS  Google Scholar 

  165. Behse F, Buchthal F, Carlsen F, Knappeis GG. Hereditary neuropathy with liability to pressure palsies: eletrophysiological and histopathological aspects. Brain. 1972;95:777–94.

    Article  PubMed  CAS  Google Scholar 

  166. Madrid R, Bradley WG. The pathology of neuropathies with focal thickening of the myelin sheath (tomaculous neuropathy). J Neurol Sci. 1975;25:415–48.

    Article  Google Scholar 

  167. Gabreels-Festen A, van de Wetering R. Human nerve pathology caused by different mutational mechanisms of the PMP22 gene. Ann N Y Acad Sci. 1999;883:336–43.

    Article  PubMed  CAS  Google Scholar 

  168. Sander S, Ouvrier RA, McLeod JG, Nicholson GA, Pollard JD. Clinical syndromes associated with tomacula or myelin swellings in sural nerve biopsies. J Neurol Neurosurg Psychiatry. 2000;68:483–8.

    Article  PubMed  CAS  Google Scholar 

  169. Ochoa J, Danta G, Fowler T, Gilliatt RW. Nature of the nerve lesion caused by a pneumatic tourniquet. Nature. 1971;233:265–6.

    Article  PubMed  CAS  Google Scholar 

  170. Vallat JM, Gil R, Leboutet MJ, Hugon J, Moulies D. Congenital hypo- and hypermyelination neuropathy. Acta Neuropathol. 1987;74:197–201.

    Article  PubMed  CAS  Google Scholar 

  171. Gabreels-Festen A, Joosten EM, et al. Congenital demyelinating motor and sensory neuropathy with focally folded myelin sheath. Brain. 1990;113:1629–43.

    Article  PubMed  Google Scholar 

  172. Thomas FP, Lebo RV, Rosoklija G, et al. Tomaculous neuropathy in chromosome 1 Charcot-Marie-Tooth syndrome. Acta Neuropathol. 1994;87:91–7.

    Article  PubMed  CAS  Google Scholar 

  173. Vital C, Pautrizel B, Lagueny A, et al. Hypermyelinisation dans un cas de neuropathie peripherique avec gammopathie monoclonale benigne a IgM. Rev Neurol. 1985;141:729–34.

    PubMed  CAS  Google Scholar 

  174. 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;46:1318–24.

    Article  PubMed  CAS  Google Scholar 

  175. Uyemura K, Asou H, Takeda Y. Structure and function of peripheral nerve myelin proteins. Prog Brain Res. 1995;105:311–8.

    Article  PubMed  CAS  Google Scholar 

  176. Birouk N, Gouider R, Le Guern E, et al. Charcot-Marie-Tooth disease type 1A with 17p11.2 duplication. Clinical and electrophysiological phenotype study and factors influencing disease severity in 119 cases. Brain. 1997;120:813–23.

    Article  PubMed  Google Scholar 

  177. Maeda MH, Mitsui J, Soong BW, Takahashi Y, Ishiura H, Hayashi S, et al. Increased gene dosage of myelin protein zero causes Charcot-Marie-Tooth disease. Ann Neurol. 2012;71:84–92.

    Article  PubMed  CAS  Google Scholar 

  178. Shy ME, Jani A, Krajewski K, et al. Phenotypic clustering in MPZ mutations. Brain. 2004;127:371–84.

    Article  PubMed  Google Scholar 

  179. Magot A, Latour P, Mussini JM, Mourtada R, Guiheneuc P, Pereon Y. A new MPZ mutation associated with a mild CMT1 phenotype presenting with recurrent nerve compression. Muscle Nerve. 2008;38:1055–9.

    Article  PubMed  CAS  Google Scholar 

  180. Schneider-Gold C, Kötting J, Epplen JT, Gold R, Gerding WM. Unusual Charcot-Marie-Tooth phenotype due to a mutation within the intracellular domain of myelin protein zero. Muscle Nerve. 2010;41:550–4.

    Article  PubMed  CAS  Google Scholar 

  181. Baloh RH, Jen JC, Kim G, Baloh RW. Chronic cough due to thr124met mutation in the peripheral myelin protein zero (MPZ gene). Neurology. 2004;62:1905–6.

    Article  PubMed  Google Scholar 

  182. Murphy SM, Laurá M, Blake J, Polke J, Bremner F, Reilly MM. Conduction block and tonic pupils in Charcot-Marie-Tooth disease caused by a myelin protein zero p.Ile112Thr mutation. Neuromuscul Disord. 2011;21:223–6.

    Article  PubMed  Google Scholar 

  183. 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. 2000;69:799–805.

    Article  PubMed  CAS  Google Scholar 

  184. Lagueny A, Latour P, Vital A, et al. Mild recurrent neuropathy in CMT1B with a novel nonsense mutation in the extracellular domain of the MPZ gene. J Neurol Neurosurg Psychiatry. 2001;70:232–5.

    Article  PubMed  CAS  Google Scholar 

  185. Plante-Bordeneuve V, Parman Y, Guiochon-Mantel A, et al. The range of chronic demyelinating neuropathy of infancy: a clinico-pathological and genetic study of 15 unrelated cases. J Neurol. 2001;248:795–803.

    Article  PubMed  CAS  Google Scholar 

  186. Sorour E, MacMillan J, Upadhyaya M. Novel mutation of the myelin P0 gene in a CMT1B family. Hum Mutat. 1997;9:74–7.

    Article  PubMed  CAS  Google Scholar 

  187. Shizuka M, Ikeda Y, Watanabe M, et al. A novel mutation of the myelin P0 gene segregating Charcot-Marie-Tooth disease type 1B manifesting as trigeminal nerve thickening. J Neurol Neurosurg Psychiatry. 1999;67:250–1.

    Article  PubMed  CAS  Google Scholar 

  188. Filbin MT, Walsh FS, Trapp BD, Pizzey JA, Tennekoon GI. Role of myelin P0 protein as a homophilic adhesion molecule. Nature. 1990;344:871–2.

    Article  PubMed  CAS  Google Scholar 

  189. Desarnaud F, Bidichandani S, Patel PI, Baulieu EE, Schumacher M. Glucocorticosteroids stimulate the activity of the promoters of peripheral myelin protein-22 and protein zero genes in Schwann cells. Brain Res. 2000;19(865):12–6.

    Article  Google Scholar 

  190. Xu W, Manichella D, Jiang H, et al. Absence of P0 leads to the dysregulation of myelin gene expression and myelin morphogenesis. J Neurosci Res. 2000;60:714–24.

    Article  PubMed  CAS  Google Scholar 

  191. Bird TD, Kraft GH, Lipe HP, Kenney KL, Sumi SM. Clinical and pathological phenotype of original family with Charcot-Marie-Tooth type 1B: a 20-year study. Ann Neurol. 1997;41:463–9.

    Article  PubMed  CAS  Google Scholar 

  192. Li J, Grandis M, Krajewski KM, et al. Clinical, pathological and molecular phenotype of a human MPZ mutation: an autopsy study. Proceedings of the first European and North American Charcot-Marie-Tooth Consortium Meeting; 2004 July 8–10; Anwerpen, Belgium; 2004.

    Google Scholar 

  193. Gabreels-Festen AA, Hoogendijk JE, Meijerink PH, et al. Two divergent types of nerve pathology in patients with different P0 mutations in Charcot-Marie-Tooth disease. Neurology. 1996;47:761–5.

    Article  PubMed  CAS  Google Scholar 

  194. Lagueny A, Latour P, Vital A, et al. Peripheral myelin modification in CMT1B correlates with MPZ gene mutations. Neuromuscul Disord. 1999;9:361–7.

    Article  PubMed  CAS  Google Scholar 

  195. Nakagawa M, Suehara M, Saito A, et al. A novel MPZ gene mutation in dominantly inherited neuropathy with focally folded myelin sheaths. Neurology. 1999;52:1271–5.

    Article  PubMed  CAS  Google Scholar 

  196. Fabrizi GM, Taioli F, Cavallaro T, et al. Focally folded myelin in Charcot-Marie-Tooth neuropathy type 1B with Ser49Leu in the myelin protein zero. Acta Neuropathol. 2000;100:299–304.

    Article  PubMed  CAS  Google Scholar 

  197. Kochanski A, Drac H, Jedrzejowska H, Hausmanowa-Petrusewicz I. Focally folded myelin in Charcot-Marie-Tooth type 1B disease is associated with Asn131Lys mutation in myelin protein zero gene: short report. Eur J Neurol. 2003;10:547–9.

    Article  PubMed  CAS  Google Scholar 

  198. Matsuyama W, Nakagawa M, Takashima H, Osame M. Altered trafficking and adhesion of MPZ mutations and phenotypes of Charcot-Marie-Tooth disease 1B. Acta Neuropathol. 2002;103:501–8.

    Article  PubMed  CAS  Google Scholar 

  199. Kirschner DA, Szumowski K, Gabreels-Festen AA, Hoogendijk JE, Bolhuis PA. Inherited demyelinating peripheral neuropathies: relating myelin packing abnormalities to P0 molecular defects. J Neurosci Res. 1996;46:502–8.

    Article  PubMed  CAS  Google Scholar 

  200. Komiyama A, Ohnishi A, Izawa K, Yamamori S, Ohashi H, Hasegawa O. De novo mutation (Arg98–>Cys) of the myelin P0 gene and uncompaction of the major dense line of the myelin sheath in a severe variant of Charcot-Marie-Tooth disease type 1B. J Neurol Sci. 1997;149:103–9.

    Article  PubMed  CAS  Google Scholar 

  201. Street VA, Bennett CL, Goldy JD. Mutation of a putative protein degradation gene LITAF/SIMPLE in Charcot-Marie-Tooth ­disease 1C. Neurology. 2003;60:22–6.

    Article  PubMed  CAS  Google Scholar 

  202. Lee SM, Olzmann JA, Chin LS, Li L. Mutations associated with Charcot-Marie-Tooth disease cause SIMPLE protein mislocalization and degradation by the proteasome and aggresome-autophagy pathways. J Cell Sci. 2011;124:3319–31.

    Article  PubMed  CAS  Google Scholar 

  203. Warner LE, Mancias P, Butler IJ, et al. Mutations in the early growth response 2 (EGR2) gene are associated with hereditary myelinopathies. Nat Genet. 1998;18:382–4.

    Article  PubMed  CAS  Google Scholar 

  204. De Jonghe P, Mersivanova I, Nelis E, et al. Further evidence that neurofilament light chain gene mutations can cause Charcot-Marie-Tooth disease type 2E. Ann Neurol. 2001;49:245–9.

    Article  PubMed  Google Scholar 

  205. Jordanova A, De Jonghe P, Boerkoel CF, et al. Mutations in the neurofilament light chain gene (NEFL) cause early onset severe Charcot-Marie-Tooth disease. Brain. 2003;126:590–7.

    Article  PubMed  CAS  Google Scholar 

  206. Yiu EM, Geevasinga N, Nicholson GA, Fagan ER, Ryan MM, Ouvrier RA. A retrospective review of X-linked Charcot-Marie-Tooth disease in childhood. Neurology. 2011;76:461–6.

    Article  PubMed  CAS  Google Scholar 

  207. Hahn AF, Brown WF, Koopman WJ, Feasby TE. X-linked dominant hereditary motor and sensory neuropathy. Brain. 1990;113:1511–25.

    Article  PubMed  Google Scholar 

  208. Hahn AF, Bolton CF, Whiate CM, et al. Genotype/phenotype correlations in X-linked Charcot-Marie-Tooth disease. Ann N Y Acad Sci. 1999;883:366–82.

    Article  PubMed  CAS  Google Scholar 

  209. Mazzeo A, Di Leo R, Toscano A, Muglia M, Patitucci A, Messina C, et al. Charcot-Marie-Tooth type X: unusual phenotype of a novel CX32 mutation. Eur J Neurol. 2008;15:1140–2.

    Article  PubMed  CAS  Google Scholar 

  210. Fain PR, Barker DF, Chance PF. Refined genetic mapping of X-linked Charcot-Marie-Tooth neuropathy. Am J Hum Genet. 1994;54:229–35.

    PubMed  CAS  Google Scholar 

  211. Le Guern E, Ravise N, Gugenheim M, et al. Linkage analyses between dominant X-linked Charcot-Marie-Tooth disease, and 15 Xq11-Xq21 microsatellites in a new large family: three new markers are closely linked to the gene. Neuromuscul Disord. 1994;4:463–9.

    Article  PubMed  Google Scholar 

  212. Birouk N, LeGuern E, et al. X-linked Charcot-Marie-Tooth disease with connexin 32 mutations: clinical and electrophysiologic study. Neurology. 1998;50:1074–82.

    Article  PubMed  CAS  Google Scholar 

  213. Nicholson G, Nash J. Intermediate nerve conduction velocities define X-linked Charcot-Marie-Tooth neuropathy families. Neurology. 1993;43:2558–64.

    Article  PubMed  CAS  Google Scholar 

  214. Ressot C, Bruzzone R. Connexin channels in Schwann cells and the development of the X-linked form of Charcot-Marie-Tooth disease. Brain Res Brain Res Rev. 2000;32:192–202.

    Article  PubMed  CAS  Google Scholar 

  215. Ionasescu VV, Trofatter J, Haines JL, Summers AM, Ionasescu R, Searby C. X-linked recessive Charcot-Marie-Tooth neuropathy: clinical and genetic study. Muscle Nerve. 1992;15:368–73.

    Article  PubMed  CAS  Google Scholar 

  216. Brewer M, Changi F, Antonellis A, Fischbeck K, Polly P, Nicholson G, et al. Evidence of a founder haplotype refines the X-linked Charcot-Marie-Tooth (CMTX3) locus to a 2.5 Mb region. Neurogenetics. 2008;9:191–5.

    Article  PubMed  CAS  Google Scholar 

  217. Cowchock FS, Duckett SW, Streletz LJ, Graziani LJ, Jackson LG. X-linked motor-sensory neuropathy type-II with deafness and mental retardation: a new disorder. Am J Med Genet. 1985;20:307–15.

    Article  PubMed  CAS  Google Scholar 

  218. Vinci P, Oliveira GR, Antenor J, Thomas FP. Anticipation in Charcot-Marie-Tooth disease type 2 (CMT2). Neurology. 2001;56 Suppl 3:A324.

    Google Scholar 

  219. Muglia M, Zappia M, Timmerman V. Clinical and genetic study of a large Charcot-Marie-Tooth type 2A family from southern Italy. Neurology. 2001;56:100–3.

    Article  PubMed  CAS  Google Scholar 

  220. Saito M, Hayashi Y, Suzuki T, Tanaka H, Hozumi I, Tsuji S. Linkage mapping of the gene for Charcot-Marie-Tooth disease type 2 to chromosome 1p (CMT2A) and the clinical features of CMT2A. Neurology. 1997;49:1630–5.

    Article  PubMed  CAS  Google Scholar 

  221. Verhoeven K, Claeys KG, Züchner S, et al. MFN2 mutation distribution and genotype /phenotype correlation in Charcot-Marie-Tooth type 2. Brain. 2006;129:2093–102.

    Article  PubMed  Google Scholar 

  222. Züchner S, Mersiyanova IV, Muglia M. Mutations in the mitochondrial GTPase mitofusin 2 cause Charcot-Marie-Tooth neuropathy type 2A. Nat Genet. 2004;36:449–51.

    Article  PubMed  CAS  Google Scholar 

  223. Lawson VH, Graham BV, Flanigan KM. Clinical and electrophysiologic features of CMT2A with mutations in the mitofusin 2 gene. Neurology. 2005;65:197–204.

    Article  PubMed  CAS  Google Scholar 

  224. Zhao C, Takita J, Tanaka Y. Charcot-Marie-Tooth disease type 2A caused by mutation in a microtubule motor KIF1Bbeta. Cell. 2001;105:587–97.

    Article  PubMed  CAS  Google Scholar 

  225. Feely SM, Laura M, Siskind CE, Sottile S, Davis M, Gibbons VS, et al. MFN2 mutations cause severe phenotypes in most patients with CMT2A. Neurology. 2011;76:1690–6.

    Article  PubMed  CAS  Google Scholar 

  226. Calvo J, Funalot B, Ouvrier RA, et al. Genotype-phenotype correlations in Charcot-Marie-Tooth disease type 2 caused by mitofusin 2 mutations. Arch Neurol. 2009;66:1511–6.

    Article  PubMed  Google Scholar 

  227. Kwon JM, Elliott JL, Yee WC, et al. Assignment of a second Charcot-Marie-Tooth type II locus to chromosome 3q. Am J Hum Genet. 1995;57:853–8.

    PubMed  CAS  Google Scholar 

  228. Verhoeven K, De Jonghe P, Coen K. Mutations in the small GTP-ase late endosomal protein RAB7 cause Charcot-Marie-Tooth type 2B neuropathy. Am J Hum Genet. 2003;72:22–7.

    Article  Google Scholar 

  229. Bouhouche A, Benomar A, Birouk N, et al. A locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 1q21.2-q21.3. Am J Hum Genet. 1999;65:722–7.

    Article  PubMed  CAS  Google Scholar 

  230. De Sandre-Giovannoli A, Chaouch M, Kozlov S, et al. Homozygous defects in LMNA, encoding lamin A/C nuclear-envelope proteins, cause autosomal recessive axonal neuropathy in human (Charcot-Marie-Tooth disorder type 2) and mouse. Am J Hum Genet. 2002;70:726–36.

    Article  PubMed  Google Scholar 

  231. Leal A, Morera B, Del Valle G, et al. A second locus for an axonal form of autosomal recessive Charcot-Marie-Tooth disease maps to chromosome 19q13.3. Am J Hum Genet. 2001;68:269–74.

    Article  PubMed  CAS  Google Scholar 

  232. Leal A, Huehne K, Bauer F, et al. Identification of the variant Ala335Val of MED25 as responsible for CMT2B2: molecular data, functional studies of the SH3 recognition motif and correlation between wild-type MED25 and PMP22 RNA levels in CMT1A animal models. Neurogenetics. 2009;10:275–87.

    Article  PubMed  CAS  Google Scholar 

  233. Deng HX, Klein CJ, Yan J, et al. Scapuloperoneal spinal muscular atrophy and CMT2C are allelic disorders caused by alterations in TRPV4. Nat Genet. 2010;42:165–9.

    Article  PubMed  CAS  Google Scholar 

  234. Landouré G, Zdebik AA, Martinez TL, et al. Mutations in TRPV4 cause Charcot-Marie-Tooth disease type 2C. Nat Genet. 2010;42:170–4.

    Article  PubMed  CAS  Google Scholar 

  235. Zimoń M, Baets J, Auer-Grumbach M, Berciano J. Dominant mutations in the cation channel gene transient receptor potential vanilloid 4 cause an unusual spectrum of neuropathies. Brain. 2010;133:1798–809.

    Article  PubMed  Google Scholar 

  236. 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. 1996;5:1373–5.

    Article  PubMed  CAS  Google Scholar 

  237. Antonellis A, Ellsworth RE, Sambuughin N, et al. Glycyl tRNA synthetase mutations in Charcot-Marie-Tooth disease type 2D and distal spinal muscular atrophy type V. Am J Hum Genet. 2003;72:1293–9.

    Article  PubMed  CAS  Google Scholar 

  238. Eskuri JM, Stanley CM, Moore SA, Mathews KD. Infantile onset CMT2D/dSMA V in monozygotic twins due to a mutation in the anticodon-binding domain of GARS. J Peripher Nerv Syst. 2012;17:132–4.

    Article  PubMed  CAS  Google Scholar 

  239. Christodoulou K, Kyriakides T, Hristova AH, et al. Mapping of a distal form of spinal muscular atrophy with upper limb predominance to chromosome 7p. Hum Mol Genet. 1995;4:1629–32.

    Article  PubMed  CAS  Google Scholar 

  240. Seburn KL, Nangle LA, Cox GA, et al. An active dominant mutation of glycyl-tRNA synthetase causes neuropathy in a Charcot-Marie-Tooth 2D mouse model. Neuron. 2006;51:715–26.

    Article  PubMed  CAS  Google Scholar 

  241. Mersiyanova IV, Perepelov AV, Polyakov AV. A new variant of Charcot-Marie-Tooth disease type 2 is probably the result of a mutation in the neurofilament-light gene. Am J Hum Genet. 2000;67:37–46.

    Article  PubMed  CAS  Google Scholar 

  242. Georgiou DM, Zidar J, Korosec M, Middleton LT, Kyriakides T, Christodoulou K. A novel NF-L mutation pro22-to-ser is associated with CMT2 in a large Slovenian family. Neurogenetics. 2002;4:93–6.

    Article  PubMed  CAS  Google Scholar 

  243. Carpenter DA, Ip W. Neurofilament triplet protein interactions: evidence for the preferred formation of NF-L-containing dimers and a putative function for the end domains. J Cell Sci. 1996;109:2493–8.

    PubMed  CAS  Google Scholar 

  244. Yum SW, Zhang J, Mo K, Li J, Scherer SS. A novel recessive NEFL mutation causes a severe, early-onset axonal neuropathy. Ann Neurol. 2009;66:759–70.

    Article  PubMed  CAS  Google Scholar 

  245. Fabrizi GM, Cavallaro T, Angiari C, et al. Charcot-Marie-Tooth disease type 2E, a disorder of the cytoskeleton. Brain. 2007;130:394–403.

    Article  PubMed  Google Scholar 

  246. Ismailov SM, Fedotov VP, Dadali EL. A new locus for autosomal dominant Charcot-Marie-Tooth disease type 2 (CMT2F) maps to chromosome 7q11-q21. Eur J Hum Genet. 2001;9:646–50.

    Article  PubMed  CAS  Google Scholar 

  247. Evgrafov OV, Mersiyanova I, Irobi J, et al. Mutant small heat-shock protein 27 causes axonal Charcot-Marie-Tooth disease and distal hereditary motor neuropathy. Nat Genet. 2004;36:602–6.

    Article  PubMed  CAS  Google Scholar 

  248. Berciano J, Combarros O, Figols J, et al. Hereditary motor and sensory neuropathy type II. Clinicopathological study of a family. Brain. 1986;109:897–914.

    Article  PubMed  Google Scholar 

  249. Nelis E, Berciano J, Verpoorten N, et al. Autosomal dominant axonal Charcot-Marie-Tooth disease type 2 (CMT2G) maps to chromosome 12q12-q13.3. J Med Genet. 2004;41:193–7.

    Article  PubMed  CAS  Google Scholar 

  250. Barhoumi C, Amouri R, Ben Hamida C. Linkage of a new locus for autosomal recessive axonal form of Charcot-Marie-Tooth ­disease to chromosome 8q21.3. Neuromuscul Disord. 2001;11:27–34.

    Article  PubMed  CAS  Google Scholar 

  251. Zimoń M, Baets J, Fabrizi GM, et al. Dominant GDAP1 mutations cause predominantly mild CMT phenotypes. Neurology. 2011;77:540–8.

    Article  PubMed  CAS  Google Scholar 

  252. 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;50:1397–401.

    Article  PubMed  CAS  Google Scholar 

  253. Senderek J, Hermanns B, Lehmann U, et al. Charcot-Marie-Tooth neuropathy type 2 and P0 point mutations: two novel amino acid substitutions (Asp61Gly; Tyr119Cys) and a possible “hotspot” on Thr124Met. Brain Pathol. 2000;10:235–48.

    Article  PubMed  CAS  Google Scholar 

  254. Auer-Grumbach M, Strasser-Fuchs S, Robl T, Windpassinger C, Wagner K. Late onset Charcot-Marie-Tooth 2 syndrome caused by two novel mutations in the MPZ gene. Neurology. 2003;61:1435–7.

    Article  PubMed  CAS  Google Scholar 

  255. Sowden JE, Logigian EL, Malik K, Herrmann DN. Genotype-phenotype correlation in a family with late onset CMT and an MPZ lys236del mutation. J Neurol Neurosurg Psychiatry. 2005;76:442–4.

    Article  PubMed  CAS  Google Scholar 

  256. 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;66:779–82.

    Article  PubMed  CAS  Google Scholar 

  257. Gallardo E, Garcia A, Ramón C, et al. Charcot-Marie-Tooth disease type 2J with MPZ Thr124Met mutation: clinico-­electrophysiological and MRI study of a family. J Neurol. 2009;256:2061–71.

    Article  PubMed  Google Scholar 

  258. Tang B, Zhao G, Luo W, et al. Small heat-shock protein 22 mutated in autosomal dominant Charcot-Marie-Tooth disease type 2L. Hum Genet. 2005;116:222–4.

    Article  PubMed  CAS  Google Scholar 

  259. Fabrizi GM, Ferrarini M, Cavallaro T, Cabrini I, Cerini R, Bertolasi L, et al. Two novel mutations in dynamin-2 cause axonal Charcot-Marie-Tooth disease. Neurology. 2007;69:291–5.

    Article  PubMed  CAS  Google Scholar 

  260. Züchner S, Noureddine M, Kennerson M, et al. Mutations in the pleckstrin homology domain of dynamin 2 cause dominant intermediate Charcot-Marie-Tooth disease. Nat Genet. 2005;37:289–94.

    Article  PubMed  CAS  Google Scholar 

  261. Zhu D, Kennerson M, Merory J, et al. Refined localization of dominant intermediate Charcot-Marie-Tooth neuropathy and exclusion of seven known candidate genes in the region. Neurogenetics. 2003;4:179–83.

    Article  PubMed  CAS  Google Scholar 

  262. McLaughlin HM, Sakaguchi R, Giblin W. A recurrent loss-of-function alanyl-tRNA synthetase (AARS) mutation in patients with Charcot-Marie-Tooth disease type 2N (CMT2N). Hum Mutat. 2012;33:244–53.

    Article  PubMed  CAS  Google Scholar 

  263. Latour P, Thauvin-Robinet C, Baudelet-Méry C, et al. A major determinant for binding and aminoacylation of tRNA(Ala) in cytoplasmic Alanyl-tRNA synthetase is mutated in dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet. 2010;86:77–82.

    Article  PubMed  CAS  Google Scholar 

  264. Weedon MN, Hastings R, Caswell R, et al. Exome sequencing identifies a DYNC1H1 mutation in a large pedigree with dominant axonal Charcot-Marie-Tooth disease. Am J Hum Genet. 2011;89:308–12.

    Article  PubMed  CAS  Google Scholar 

  265. Weterman MA, Sorrentino V, Kasher PR, et al. A frameshift mutation in LRSAM1 is responsible for a dominant hereditary polyneuropathy. Hum Mol Genet. 2012;21:358–70.

    Article  PubMed  CAS  Google Scholar 

  266. Guernsey DL, Jiang H, Bedard K, et al. Mutation in the gene encoding ubiquitin ligase LRSAM1 in patients with Charcot-Marie-Tooth disease. PLoS Genet. 2010;6:e1001081.

    Article  PubMed  CAS  Google Scholar 

  267. Plante-Bordeneuve V, Said G. Dejerine-Sottas disease and hereditary demyelinating polyneuropathy of infancy. Muscle Nerve. 2002;26:608–21.

    Article  PubMed  CAS  Google Scholar 

  268. Takashima H, Boerkoel CF, De Jonghe P, et al. Periaxin mutations cause a broad spectrum of demyelinating neuropathies. Ann Neurol. 2002;51:709–15.

    Article  PubMed  CAS  Google Scholar 

  269. Ionasescu VV, Kimura J, Searby CC, et al. A Dejerine-Sottas neuropathy family with a gene mapped on chromosome 8. Muscle Nerve. 1996;19:319–23.

    Article  PubMed  CAS  Google Scholar 

  270. Harati Y, Butler IJ. Congenital hypomyelinating neuropathy. J Neurol Neurosurg Psychiatry. 1985;48:1269–76.

    Article  PubMed  CAS  Google Scholar 

  271. Fabrizi GM, Simonati A, Taioli F, et al. PMP22 related congenital hypomyelination neuropathy. J Neurol Neurosurg Psychiatry. 2001;70:123–6.

    Article  PubMed  CAS  Google Scholar 

  272. Dreschfeld J. On some rarer forms of muscular atrophies. Brain. 1886;79:226–32.

    Google Scholar 

  273. Jacob JC, Andermann F, Robb JP. Heredofamilial neuritis with brachial predilection. Neurology. 1961;11:1025–33.

    Article  PubMed  CAS  Google Scholar 

  274. Guillozet N, Mercer RD. Hereditary recurrent brachial neuropathy. Am J Dis Child. 1973;125:884–7.

    PubMed  CAS  Google Scholar 

  275. Meuleman J, Timmerman V, Van Broeckhoven C. Hereditary neuralgic amyotrophy. Neurogenetics. 2001;3:115–8.

    Article  PubMed  CAS  Google Scholar 

  276. van Alfen N, van Engelen BG. The clinical spectrum of neuralgic amyotrophy in 246 cases. Brain. 2006;129:438–50.

    Article  PubMed  Google Scholar 

  277. Jeannet PY, Watts GD, Bird TD. Craniofacial and cutaneous findings expand the phenotype of hereditary neuralgic amyotrophy. Neurology. 2001;57:1963–8.

    Article  PubMed  CAS  Google Scholar 

  278. Kuhlenbäumer G, Hannibal MC, Nelis E, Schirmacher A, et al. Mutations in SEPT9 cause hereditary neuralgic amyotrophy. Nat Genet. 2005;37:1044–6.

    Article  PubMed  CAS  Google Scholar 

  279. 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;2:1625–8.

    Article  PubMed  CAS  Google Scholar 

  280. Nelis E, Erdem S, Van Den Bergh PY, et al. Mutations in GDAP1: autosomal recessive CMT with demyelination and axonopathy. Neurology. 2002;59:1865–72.

    Article  PubMed  CAS  Google Scholar 

  281. Baxter RV, Ben Othmane K, Rochelle JM, et al. Ganglioside-induced differentiation-associated protein-1 is mutant in Charcot-Marie-Tooth disease type 4A/8q21. Nat Genet. 2002;30:21–2.

    Article  PubMed  CAS  Google Scholar 

  282. Senderek J, Bergmann C, Ramaekers VT, et al. Mutations in the ganglioside-induced differentiation-associated protein-1 (GDAP1) gene in intermediate type autosomal recessive Charcot-Marie-Tooth neuropathy. Brain. 2003;126:642–9.

    Article  PubMed  Google Scholar 

  283. Sevilla T, Cuesta A, Chumillas MJ, et al. Clinical, electrophysiological and morphological findings of Charcot-Marie-Tooth neuropathy with vocal cord palsy and mutations in the GDAP1 gene. Brain. 2003;126:1–11.

    Article  Google Scholar 

  284. Sevilla T, Jaijo T, Nauffal D, et al. Vocal cord paresis and diaphragmatic dysfunction are severe and frequent symptoms of GDAP1-associated neuropathy. Brain. 2008;131:3051–61.

    Article  PubMed  Google Scholar 

  285. Cuesta A, Pedrola L, Sevilla T, et al. The gene encoding ganglioside-induced differentiation-associated protein 1 is mutated in axonal Charcot-Marie-Tooth type 4A disease. Nat Genet. 2002;30:22–5.

    Article  PubMed  CAS  Google Scholar 

  286. Boerkoel CF, Takashima H, Nakagawa M, et al. CMT4A: identification of a Hispanic GDAP1 founder mutation. Ann Neurol. 2003;53:400–5.

    Article  PubMed  CAS  Google Scholar 

  287. Bolino A, Brancolini V, Bono F, et al. Localization of a gene responsible for autosomal recessive demyelinating neuropathy with focally folded myelin sheaths to chromosome 11q23 by homozygosity mapping and haplotype sharing. Hum Mol Genet. 1996;5:1051–4.

    Article  PubMed  CAS  Google Scholar 

  288. 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;50:799–801.

    Article  PubMed  CAS  Google Scholar 

  289. Bolino A, Muglia M, Conforti F, et al. Charcot-Marie-Tooth type 4B is caused by mutations in the gene encoding myotubularin-related protein-2. Nat Genet. 2000;25:17–9.

    Article  PubMed  CAS  Google Scholar 

  290. Azzedine H, Bolino A, Taieb T, et al. Mutations in MTMR13, a new pseudophosphatase homologue of MTMR2 and Sbf1, in two families with an autosomal recessive demyelinating form of Charcot-Marie-Tooth disease associated with early-onset glaucoma. Am J Hum Genet. 2003;72:1141–53.

    Article  PubMed  CAS  Google Scholar 

  291. Senderek J, Bergmann C, Weber S, et al. Mutation of the SBF2 gene, encoding a novel member of the myotubularin family, in Charcot-Marie-Tooth neuropathy type 4B2/11p15. Hum Mol Genet. 2003;12:349–56.

    Article  PubMed  CAS  Google Scholar 

  292. LeGuern E, Guilbot A, Kessali M, et al. Homozygosity mapping of an autosomal recessive form of demyelinating Charcot-Marie-Tooth disease to chromosome 5q23-q33. Hum Mol Genet. 1996;5:1685–8.

    Article  PubMed  CAS  Google Scholar 

  293. Azzedine H, Ravise N, Verny C, et al. Spine deformities in Charcot-Marie-Tooth 4C caused by SH3TC2 gene mutations. Neurology. 2006;67:602–6.

    Article  PubMed  CAS  Google Scholar 

  294. Senderek J, Bergmann C, Stendel C, et al. Mutations in a gene encoding a novel SH3/TPR domain protein cause autosomal recessive Charcot-Marie-Tooth type 4C neuropathy. Am J Hum Genet. 2003;73:1106–19.

    Article  PubMed  CAS  Google Scholar 

  295. Guilbot A, Ravise N, Bouhouche A, et al. Genetic, cytogenetic and physical refinement of the autosomal recessive CMT linked to 5q31-q33: exclusion of candidate genes including EGR1. Eur J Hum Genet. 1999;7:849–59.

    Article  PubMed  CAS  Google Scholar 

  296. Lupski JR, Reid JG, Gonzaga-Jauregui C, et al. Whole-genome sequencing in a patient with Charcot–Marie–Tooth neuropathy. N Engl J Med. 2010;362:1181–91.

    Article  PubMed  CAS  Google Scholar 

  297. Kalaydjieva L, Gresham D, Gooding R. N-myc downstream-regulated gene 1 is mu-tated in hereditary motor and sensory neuropathy-Lom. Am J Hum Genet. 2000;67:47–58.

    Article  PubMed  CAS  Google Scholar 

  298. King RH, Tournev I, Colomer J, Merlini L, Kalaydjieva L, Thomas PK. Ultrastructural changes in peripheral nerve in hereditary motor and sensory neuropathy-Lom. Neuropathol Appl Neurobiol. 1999;25:306–12.

    Article  PubMed  CAS  Google Scholar 

  299. Hunter M, Bernard R, Freitas E, et al. Mutation screening of the N-myc downstream-regulated gene 1 (NDRG1) in patients with Charcot-Marie-Tooth disease. Hum Mutat. 2003;22:129–35.

    Article  PubMed  CAS  Google Scholar 

  300. Timmerman V, De Jonghe P, Ceuterick C, et al. Novel missense mutation in the early growth response 2 (EGR2) gene associated with Dejerine-Sottas phenotype. Neurology. 1999;52:1827–32.

    Article  PubMed  CAS  Google Scholar 

  301. Kabzinska D, Drac H, Sherman DL, et al. Charcot-Marie-Tooth type 4F disease caused by S399fsx410 mutation in the PRX gene. Neurology. 2006;66:745–7.

    Article  PubMed  CAS  Google Scholar 

  302. Boerkoel CF, Takashima H, Stankiewicz P, et al. Periaxin mutations cause recessive Dejerine-Sottas neuropathy. Am J Hum Genet. 2001;68:325–33.

    Article  PubMed  CAS  Google Scholar 

  303. Guilbot A, Williams A, Ravise N, et al. A mutation in periaxin is responsible for CMT4F, an autosomal recessive form of Charcot-Marie-Tooth disease. Hum Mol Genet. 2001;10:415–21.

    Article  PubMed  CAS  Google Scholar 

  304. Thomas PK, Kalaydjieva L, Youl B, Rogers T, Angelicheva D, King RHM, et al. Hereditary motor and sensory neuropathy-russe: new autosomal recessive neuropathy in Balkan Gypsies. Ann Neurol. 2001;50:452–7.

    Article  PubMed  CAS  Google Scholar 

  305. Rogers T, Chandler D, Angelicheva D, et al. A novel locus for autosomal recessive peripheral neuropathy in the EGR2 region on 10q23. Am J Hum Genet. 2000;67:664–71.

    Article  PubMed  CAS  Google Scholar 

  306. Hantke J, Chandler D, King R, et al. A mutation in an alternative untranslated exon of hexokinase 1 associated with hereditary motor and sensory neuropathy – Russe (HMSNR). Eur J Hum Genet. 2009;17:1606–14.

    Article  PubMed  CAS  Google Scholar 

  307. De Sandre-Giovannoli A, Delague V, Hamadouche T, et al. Homozygosity mapping of autosomal recessive demyelinating Charcot-Marie-Tooth neuropathy (CMT4H) to a novel locus on chromosome 12p11.21-q13.11. J Med Genet. 2005;42:260–5.

    Article  PubMed  CAS  Google Scholar 

  308. Delague V, Jacquier A, Hamadouche T, et al. Mutations in FGD4 encoding the Rho GDP/GTP exchange factor FRABIN cause autosomal recessive Charcot-Marie-Tooth type 4H. Am J Hum Genet. 2007;81:1–16.

    Article  PubMed  CAS  Google Scholar 

  309. Fabrizi GM, Taioli F, Cavallaro T, et al. Further evidence that mutations in FGD4/frabin cause Charcot-Marie-Tooth disease type 4H. Neurology. 2009;72:1160–4.

    Article  PubMed  CAS  Google Scholar 

  310. Houlden H, Hammans S, Katifi H, Reilly MM. A novel Frabin (FGD4) nonsense mutation p.R275X associated with phenotypic variability in CMT4H. Neurology. 2009;72:617–20.

    Article  PubMed  CAS  Google Scholar 

  311. Chow CY, Zhang Y, Dowling JJ, et al. Mutation of FIG 4 causes neurodegeneration in the pale tremor mouse and patients with CMT4J. Nature. 2007;448:68–72.

    Article  PubMed  CAS  Google Scholar 

  312. Nicholson G, Lenk GM, Reddel SW, et al. Distinctive genetic and clinical features of CMT4J: a severe neuropathy caused by mutations in the PI(3,5)P2 phosphatase FIG 4. Brain. 2011;134:1959–71.

    Article  PubMed  Google Scholar 

  313. Bomont P, Cavalier L, Blondeau F, et al. The gene encoding gigaxonin, a new member of the cytoskeletal BTB/kelch repeat family, is mutated in giant axonal neuropathy. Nat Genet. 2000;26:370–4.

    Article  PubMed  CAS  Google Scholar 

  314. Timmerman V, De Jonghe P, Spoelders P, et al. Linkage and mutation analysis of Charcot-Marie-Tooth neuropathy type 2 families with chromosomes 1p35-p36 and Xq13. Neurology. 1996;46:1311–8.

    Article  PubMed  CAS  Google Scholar 

  315. Fabrizi GM, Cavallaro T, Angiari C, Bertolasi L, Cabrini I, Ferrarini M, et al. Giant axon and neurofilament accumulation in Charcot–Marie–Tooth disease type 2E. Neurology. 2004;62:1429–31.

    Article  PubMed  CAS  Google Scholar 

  316. Züchner S, Vorgerd M, Sindern E, Schroder JM. The novel neurofilament light (NEFL) mutation Glu397Lys is associated with a clinically and morphologically heterogeneous type of Charcot-Marie-Tooth neuropathy. Neuromuscul Disord. 2004;14:147–57.

    Article  PubMed  Google Scholar 

  317. 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;232:91–8.

    Article  PubMed  CAS  Google Scholar 

  318. Malandrini A, Ceuterick C, Villanova M, et al. Ultrastructural findings in the peripheral nerve in a family with the intermediate form of Charcot-Marie-Tooth disease. J Submicrosc Cytol Pathol. 2001;33:59–63.

    PubMed  CAS  Google Scholar 

  319. Villanova M, Timmerman V, De Jonghe P, et al. Charcot-Marie-Tooth disease: an intermediate form. Neuromuscul Disord. 1998;8:392–3.

    Article  PubMed  CAS  Google Scholar 

  320. Verhoeven K, Villanova M, Rossi A. Localization of the gene for the intermediate form of Charcot-Marie-Tooth to chromosome 10q24.1-q25.1. Am J Hum Genet. 2001;69:889–94.

    Article  PubMed  CAS  Google Scholar 

  321. Kennerson ML, Zhu D, Gardner RJ. Dominant intermediate Charcot-Marie-Tooth neuropathy maps to chromosome 19p12-p13.2. Am J Hum Genet. 2001;69:883–8.

    Article  PubMed  CAS  Google Scholar 

  322. Claeys KG, Züchner S, Kennerson M, et al. Phenotypic spectrum of dynamin 2 mutations in Charcot-Marie-Tooth neuropathy. Brain. 2009;132:1741–52.

    Article  PubMed  Google Scholar 

  323. Speer MC, Graham FL, Bonner E, Collier K, Stajich JM, Gaskell PC, et al. Reduction in the minimum candidate interval in the dominant-intermediate form of Charcot-Marie-Tooth neuropathy to D19S586 to D19S432. Neurogenetics. 2002;4:83–5.

    Article  PubMed  Google Scholar 

  324. Thomas FP, Gondim F, Kinsella LJ, et al. A novel autosomal dominant polyneuropathy with intermediate conduction velocities: a clinical, electrodiagnostic, morphologic and gene linkage study of 21 affected and 44 unaffected adults and children from an 8 generation pedigree. Neurology. 2001;56 Suppl 3:A315.

    Google Scholar 

  325. Jordanova A, Thomas FP, Guergueltcheva V, et al. Dominant intermediate Charcot-Marie-Tooth type C maps to chromosome 1p34-p35. Am J Hum Genet. 2003;73:1423–30.

    Article  PubMed  CAS  Google Scholar 

  326. Jordanova A, Irobi J, Thomas FP, et al. Disrupted function and axonal distribution of mutant tyrosyl-tRNA synthetase in dominant intermediate Charcot-Marie-Tooth neuropathy. Nat Genet. 2006;38:197–202.

    Article  PubMed  CAS  Google Scholar 

  327. Storkebaum E, Leitão-Gonçalves R, Godenschwege T, et al. Dominant mutations in the tyrosyl-tRNA synthetase gene recapitulate in Drosophila features of human Charcot-Marie-Tooth neuropathy. Proc Natl Acad Sci U S A. 2009;106:11782–7.

    Article  PubMed  CAS  Google Scholar 

  328. Boyer O, Nevo F, Plaisier E, et al. INF2 mutations in Charcot-Marie-Tooth disease with glomerulopathy. N Engl J Med. 2011;365:2377–88.

    Article  PubMed  CAS  Google Scholar 

  329. McLaughlin HM, Sakaguchi R, Liu C, et al. Compound heterozygosity for loss-of-function lysyl-tRNA synthetase mutations in a patient with peripheral neuropathy. Am J Hum Genet. 2010;87:560–6.

    Article  PubMed  CAS  Google Scholar 

  330. Vinci P, Serrao M, Millul A, et al. Quality of life in patients with Charcot-Marie-Tooth disease. Neurology. 2005;65:922–4.

    Article  PubMed  CAS  Google Scholar 

  331. Odaka M, Yuki N, Kokubun N, Hirata K, Kuwabara S. Axonal Guillain-Barre syndrome associated with axonal Charcot-Marie-Tooth disease. J Neurol Sci. 2003;211:93–7.

    Article  PubMed  Google Scholar 

  332. Burns J, Ouvrier R, Estilow T, et al. Validation of the Charcot–Marie–Tooth disease pediatric scale as an outcome measure of disability. Ann Neurol. 2012;71:642–52.

    Article  PubMed  Google Scholar 

  333. De Vos A, Sermon K, Van de Velde H, et al. Pregnancy after preimplantation genetic diagnosis for Charcot-Marie-Tooth disease type 1A. Mol Hum Reprod. 1998;4:978–84.

    Article  PubMed  Google Scholar 

  334. Lebo RV. Prenatal diagnosis of Charcot-Marie-Tooth disease. Prenat Diagn. 1998;18(2):169–72.

    Article  PubMed  CAS  Google Scholar 

  335. Bernard R, Boyer A, Negre P, et al. Prenatal detection of the 17p11.2 duplication in Charcot-Marie-Tooth disease type 1A: necessity of a multidisciplinary approach for heterogeneous disorders. Eur J Hum Genet. 2002;10:297–302.

    Article  PubMed  CAS  Google Scholar 

  336. Graf WD, Chance PF, Lensch MW, Eng LJ, Lipe HP, Bird TD. Severe vincristine neuropathy in Charcot-Marie-Tooth disease type 1A. Cancer. 1996;77:1356–62.

    Article  PubMed  CAS  Google Scholar 

  337. Chauvenet AR, Shashi V, Selsky C, Morgan E, Kurtzberg J, Bell B. Vincristine-induced neuropathy as the initial presentation of Charcot-Marie-Tooth disease in acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2003;25:316–20.

    Article  PubMed  Google Scholar 

  338. Vinci P, Esposito C, Perelli SL, Antenor JA, Thomas FP. Overwork weakness in Charcot-Marie-Tooth disease. Arch Phys Med Rehabil. 2003;84:825–7.

    Article  PubMed  Google Scholar 

  339. Antognini JF. Anaesthesia for Charcot-Marie-Tooth disease: a review of 86 cases. Can J Anaesth. 1992;39:398–400.

    Article  PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Department of Neurology and Psychiatry, Institute for Molecular Virology, Saint Louis University School of Medicine, 1438 South Grand Boulevard, St. Louis, MO, 63104, USA

    Florian P. Thomas MD, MA, PhD, FAAN, FANA

  2. Department of Neurology, University Hospital Alexandrovska, Medical University-Sofia, Sofia, Bulgaria

    Velina Guergueltcheva MD, PhD

  3. Division of Neurology, Departamento de Medicina Clínica, Universidade Federal do Ceará, Faculty of Medicine Christus, Fortaleza, Ceará, Brazil

    Francisco De Assis Aquino Gondim MD, PhD, FAAN

  4. Departamento de Medicina Clínica, Universidade Federal do Ceará, Centro de Ciências da Saúde, Fortaleza, Ceará, Brazil

    Francisco De Assis Aquino Gondim MD, PhD, FAAN

  5. Department of Molecular Genetics, Molecular Neurogenomics Group, VIB and University of Antwerp, Antwerpen, Belgium

    Albena Jordanova PhD

  6. Department of Chemistry and Biochemistry, Molecular Medicine Center, Medical University-Sofia, Sofia, Bulgaria

    Albena Jordanova PhD

Authors
  1. Florian P. Thomas MD, MA, PhD, FAAN, FANA
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  2. Velina Guergueltcheva MD, PhD
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  3. Francisco De Assis Aquino Gondim MD, PhD, FAAN
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  4. Albena Jordanova PhD
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Corresponding author

Correspondence to Florian P. Thomas MD, MA, PhD, FAAN, FANA .

Editor information

Editors and Affiliations

  1. School of Medicine Department of Neurology, University Hospitals Case Medical Center Case Western Reserve University, Cleveland, Ohio, USA

    Bashar Katirji

  2. Department of Neurology, George Washington University, Washington, District of Columbia, USA

    Henry J. Kaminski

  3. University School of Medicine Department of Neurology, Louis Stokes Cleveland VA Medical Center Case Western Reserve, Cleveland, Ohio, USA

    Robert L. Ruff

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© 2014 Springer Science+Business Media New York

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Thomas, F.P., Guergueltcheva, V., De Assis Aquino Gondim, F., Jordanova, A. (2014). Charcot-Marie-Tooth Diseases. In: Katirji, B., Kaminski, H., Ruff, R. (eds) Neuromuscular Disorders in Clinical Practice. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-6567-6_26

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  • DOI: https://doi.org/10.1007/978-1-4614-6567-6_26

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  • Publisher Name: Springer, New York, NY

  • Print ISBN: 978-1-4614-6566-9

  • Online ISBN: 978-1-4614-6567-6

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