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Disorders of Pulmonary Function, Sleep, and the Upper Airway in Charcot-Marie-Tooth Disease

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Abstract

Charcot-Marie Tooth disease (CMT) encompasses several inherited peripheral motor-sensory neuropathies and is one of the most common inherited neuromuscular diseases. Charcot–Marie–Tooth disease can be associated with several disorders that may be encountered by the pulmonary physician, including restrictive pulmonary impairment, sleep apnea, restless legs, and vocal cord dysfunction. Restrictive pulmonary impairment has been described in association with phrenic nerve dysfunction, diaphragm dysfunction, or thoracic cage abnormalities. Central sleep apnea may be associated with diaphragm dysfunction and hypercapnia, whereas obstructive sleep apnea has been reported as possibly due to a pharyngeal neuropathy. Restless legs and periodic limb movement during sleep are found in a large proportion of patients with CMT2, a type of CMT associated with prominent axonal atrophy. Vocal cord dysfunction, possibly due to laryngeal nerve involvement, is found in association with several CMT types and can often mimic asthma. There may be special therapeutic considerations for the treatment of those conditions in individuals with CMT. For instance, bilevel positive airway pressure may be more appropriate than continuous positive airway pressure (CPAP) for the treatment of sleep apnea in the individual with concomitant restrictive pulmonary impairment. The prominence of peripheral neuropathy as a cause of the restless legs syndrome in CMT may justify treatment with neuropathic medications as opposed to the more commonly recommended dopaminergic agents. The risk of progression to bilateral vocal cord dysfunction in CMT and the risk of aspiration with laryngeal neuropathy may limit the therapeutic options available for vocal cord paralysis.

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Abbreviations

CMAP:

Compound muscle action potential

CMT:

Charcot–Marie–Tooth

FVC:

Forced vital capacity

MEP:

Maximal expiratory pressure

MIP:

Maximal inspiratory pressures

RLS:

Restless legs syndrome

PLMS:

Periodic leg movements during sleep

References

  1. A Consensus Conference Report (1999) Clinical indications for noninvasive positive pressure ventilation in chronic respiratory failure due to restrictive lung disease, COPD, and nocturnal hypoventilation. Chest 116:521–534

    Article  Google Scholar 

  2. Akiba Y, Kimura T, Kitaoka T, et al. (1996) [Respiratory disorders in type-1 hereditary motor and sensory neuropathy]. Nihon Kyobu Shikkan Gakkai Zasshi 34:850–855

    PubMed  CAS  Google Scholar 

  3. Anand N, Levine DB, Burke S, Bansal M (1997) Neuropathic spinal arthropathy in Charcot-Marie-Tooth disease. A case report. J Bone Joint Surg Am 79:1235–1239

    PubMed  CAS  Google Scholar 

  4. Aviv JE, Kaplan ST, Thomson JE, et al. (2000) The safety of flexible endoscopic evaluation of swallowing with sensory testing (FEESST): an analysis of 500 consecutive evaluations. Dysphagia 15:39–44

    PubMed  CAS  Google Scholar 

  5. Bach JR (1994) Update and perspective on noninvasive respiratory muscle aids. Part 2: The expiratory aids. Chest 105:1538–1544

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  7. Carter GT, Kilmer DD, Bonekat HW, Lieberman JS, Fowler WM Jr (1992) Evaluation of phrenic nerve and pulmonary function in hereditary motor and sensory neuropathy, type I. Muscle Nerve 15:459–462

    Article  PubMed  CAS  Google Scholar 

  8. Carvalho AA, Vital A, Ferrer X, et al. (2005) Charcot-Marie-Tooth disease type 1A: clinicopathological correlations in 24 patients. J Peripher Nerv Syst 10:85–92

    Article  PubMed  Google Scholar 

  9. Celik M, Forta H, Parman Y, et al. (2001) Charcot-Marie-Tooth disease associated with Type 2 diabetes mellitus. Diabet Med 18:685–686

    Article  PubMed  CAS  Google Scholar 

  10. Chan CK, Mohsenin V, Loke J, et al. (1987) Diaphragmatic dysfunction in siblings with hereditary motor and sensory neuropathy (Charcot–Marie–Tooth disease). Chest 91:567–570

    PubMed  CAS  Google Scholar 

  11. Cruz-Martinez A, Armijo A, Fermoso A, et al. (2000) Phrenic nerve conduction study in demyelinating neuropathies and open-heart surgery. Clin Neurophysiol 111:821–825

    Article  PubMed  CAS  Google Scholar 

  12. Dematteis M, Pepin JL, Jeanmart M, et al. (2001) Charcot-Marie-Tooth disease and sleep apnoea syndrome: a family study. Lancet 357:267–272

    Article  PubMed  CAS  Google Scholar 

  13. Dray TG, Robinson LR, Hillel AD (1999) Laryngeal electromyographic findings in Charcot-Marie-Tooth disease type II. Arch Neurol 56:863–865

    Article  PubMed  CAS  Google Scholar 

  14. Dyck PJ, Low PA, Stevens JC (1983) “Burning feet” as the only manifestation of dominantly inherited sensory neuropathy. Mayo Clin Proc 58:426–429

    PubMed  CAS  Google Scholar 

  15. Dyck PJ, Litchy WJ, Minnerath S, et al. (1994) Hereditary motor and sensory neuropathy with diaphragm and vocal cord paresis. Ann Neurol 35:608–615

    Article  PubMed  CAS  Google Scholar 

  16. Eichacker PQ, Spiro A, Sherman M, et al. (1988) Respiratory muscle dysfunction in hereditary motor sensory neuropathy, type I. Arch Intern Med 148:1739–1740

    Article  PubMed  CAS  Google Scholar 

  17. Entezari-Taher M, Singleton JR, Jones CR, et al. (1999) Changes in excitability of motor cortical circuitry in primary restless legs syndrome. Neurology 53:1201–1205

    PubMed  CAS  Google Scholar 

  18. Gabreels-Festen A, van Beersum S, Eshuis L, et al. (1999) Study on the gene and phenotypic characterisation of autosomal recessive demyelinating motor and sensory neuropathy (Charcot-Marie-Tooth disease) with a gene locus on chromosome 5q23-q33. J Neurol Neurosurg Psychiatry 66:569–574

    PubMed  CAS  Google Scholar 

  19. Gemignani F, Marbini A, Di Giovanni G, Salih S, Terzano MG (1999) Charcot-Marie-Tooth disease type 2 with restless legs syndrome. Neurology 52:1064–1066

    PubMed  CAS  Google Scholar 

  20. Gilchrist D, Chan CK, Deck JH (1989) Phrenic involvement in Charcot-Marie-Tooth disease. A pathologic documentation. Chest 96:1197–1199

    PubMed  CAS  Google Scholar 

  21. Hardie R, Harding AE, Hirsch N, et al. (1990) Diaphragmatic weakness in hereditary motor and sensory neuropathy. J Neurol Neurosurg Psychiatry 53:348–350

    PubMed  CAS  Google Scholar 

  22. Hensinger RN, MacEwen GD (1976) Spinal deformity associated with heritable neurological conditions: spinal muscular atrophy, Friedreich’s ataxia, familial dysautonomia, and Charcot-Marie-Tooth disease. J Bone Joint Surg Am 58:13–24

    PubMed  CAS  Google Scholar 

  23. Hill NS (2000) Management of noninvasive ventilation. In: Hill NS (ed) Long-term mechanical ventilation. Marcel Dekker, Inc., New york, pp 253–303

    Google Scholar 

  24. Iannaccone S, Zucconi M, Marchettini P, et al. (1995) Evidence of peripheral axonal neuropathy in primary restless legs syndrome. Mov Disord 10:2–9

    Article  PubMed  CAS  Google Scholar 

  25. Lacy PD, Hartley BE, Rutter MJ, Cotton RT (2001) Familial bilateral vocal cord paralysis and Charcot–Marie–tooth disease type II-C. Arch Otolaryngol Head Neck Surg 127:322–324

    PubMed  CAS  Google Scholar 

  26. Lewis RA, Sumner AJ, Shy ME (2000) Electrophysiological features of inherited demyelinating neuropathies: A reappraisal in the era of molecular diagnosis. Muscle Nerve 23:1472–1487

    Article  PubMed  CAS  Google Scholar 

  27. Mersiyanova IV, Ismailov SM, Polyakov AV, et al. (2000) Screening for mutations in the peripheral myelin genes PMP22, MPZ and Cx32 (GJB1) in Russian Charcot-Marie-Tooth neuropathy patients. Hum Mutat 15:340–347

    Article  PubMed  CAS  Google Scholar 

  28. Nathanson BN, Yu DG, Chan CK (1989) Respiratory muscle weakness in Charcot-Marie-Tooth disease. A field study. Arch Intern Med 149:1389–1391

    Article  PubMed  CAS  Google Scholar 

  29. Ondo W, Jankovic J (1996) Restless legs syndrome: clinicoetiologic correlates. Neurology 47:1435–1441

    PubMed  CAS  Google Scholar 

  30. Osanai S, Akiba Y, Nakano H, et al. (1992) Charcot-Marie-Tooth disease with diaphragmatic weakness. Intern Med 31:1267–1270

    PubMed  CAS  Google Scholar 

  31. Ota T, Osawa K (2003) Marked improvement of glycaemic control with pioglitazone in a Type 2 diabetic patient associated with Charcot-Marie-Tooth disease. Diabet Med 20:420–421

    Article  PubMed  CAS  Google Scholar 

  32. Phillips MF, Steer HM, Soldan JR, Wiles CM, Harper PS (1999) Daytime somnolence in myotonic dystrophy. J Neurol 246:275–282

    Article  PubMed  CAS  Google Scholar 

  33. Pogson D, Johnston S (2001) Anaesthesia and sleep apnoea. Br J Anaesth 87:153

    Article  PubMed  CAS  Google Scholar 

  34. Polydefkis M, Allen RP, Hauer P, et al. (2000) Subclinical sensory neuropathy in late-onset restless legs syndrome. Neurology 55:1115–1121

    PubMed  CAS  Google Scholar 

  35. Ries AL (1989) Measurement of lung volumes. Clin Chest Med 10:177–186

    PubMed  CAS  Google Scholar 

  36. Rubinsztein JS, Rubinsztein DC, Goodburn S, Holland AJ (1998) Apathy and hypersomnia are common features of myotonic dystrophy. J Neurol Neurosurg Psychiatry 64:510–515

    Article  PubMed  CAS  Google Scholar 

  37. Sagliocco L, Orlandi G, Calabrese R, et al. (2003) Electrodiagnostic evidence of phrenic nerve demyelination in Charcot-Marie-Tooth disease 1A. Am J Phys Med Rehabil 82:754–759

    Article  PubMed  Google Scholar 

  38. Santoro L, Manganelli F, Di Maio L, et al. (2002) Charcot-Marie-Tooth disease type 2C: a distinct genetic entity. Clinical and molecular characterization of the first European family. Neuromuscul Disord 12:399–404

    Article  PubMed  CAS  Google Scholar 

  39. Shy ME (2004) Charcot-Marie-Tooth disease: an update. Curr Opin Neurol 17:579–585

    Article  PubMed  CAS  Google Scholar 

  40. Stojkovic T, Latour P, Viet G, et al. (2004) Vocal cord and diaphragm paralysis, as clinical features of a French family with autosomal recessive Charcot-Marie-Tooth disease, associated with a new mutation in the GDAP1 gene. Neuromuscul Disord 14:261–264

    Article  PubMed  Google Scholar 

  41. Sulica L, Blitzer A, Lovelace RE, Kaufmann P (2001) Vocal fold paresis of Charcot-Marie-Tooth disease. Ann Otol Rhinol Laryngol 110:1072–1076

    PubMed  CAS  Google Scholar 

  42. Takakura Y, Furuya H, Yamashita K, et al. (2002) [A case of Charcot-Marie-Tooth disease (CMT) type 1 complicated by diabetes mellitus (DM) showing bilateral phrenic nerve palsy]. Rinsho Shinkeigaku 42:320–322

    PubMed  Google Scholar 

  43. Thomas PK, King RH, Bradley JL (1997) Hypertrophic neuropathy: atypical appearances resulting from the combination of type I hereditary motor and sensory neuropathy and diabetes mellitus. Neuropathol Appl Neurobiol 23:348–351

    Article  PubMed  CAS  Google Scholar 

  44. Tusiewicz K, Moldofsky H, Bryan AC, Bryan MH (1977) Mechanics of the rib cage and diaphragm during sleep. J Appl Physiol 43:600–602

    PubMed  CAS  Google Scholar 

  45. Walker JL, Nelson KR, Stevens DB, Lubicky JP, Ogden JA, VandenBrink KD (1994) Spinal deformity in Charcot-Marie-Tooth disease. Spine 19:1044–1047

    Article  PubMed  CAS  Google Scholar 

  46. Zuchner S, De Jonghe P, Jordanova A, et al. (2006) Axonal neuropathy with optic atrophy is caused by mutations in mitofusin 2. Ann Neurol 59:276–281

    Article  PubMed  CAS  Google Scholar 

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Author information

Authors and Affiliations

  1. Department of Pulmonary & Critical Care Medicine, Cleveland Clinic Foundation, 26900 Cedar Road, Suite 325-S, Beachwood, Ohio, 44122, USA

    Loutfi S. Aboussouan

  2. Department of Neurology, Wayne State University, School of Medicine, 4201 St Antoine, UHC 8D, Detroit, Michigan, 48201, USA

    Richard A. Lewis

  3. Department of Neurology and Molecular Genetics, Wayne State University, School of Medicine, 421 East Canfield, Elliman Building 3206, Detroit, Michigan, 48201, USA

    Michael E. Shy

Authors
  1. Loutfi S. Aboussouan
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  2. Richard A. Lewis
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  3. Michael E. Shy
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Correspondence to Loutfi S. Aboussouan.

Additional information

This work was supported in part by a grant from the Charcot–Marie–Tooth Association.

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Aboussouan, L.S., Lewis, R.A. & Shy, M.E. Disorders of Pulmonary Function, Sleep, and the Upper Airway in Charcot-Marie-Tooth Disease. Lung 185, 1–7 (2007). https://doi.org/10.1007/s00408-006-0053-9

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