• 1

    Kelly M: De Arthritide Symptomatica of William Musgrave (1657-1721): his description of neuropathic arthritis. Bull Hist Med 37: 372, 1963.

    • Search Google Scholar
    • Export Citation
  • 2

    Hartemann-Heurtier A, Van GH, Grimaldi A: The Charcot foot. Lancet 360: 1776, 2002.

  • 3

    Connors JC, Hardy MA, Kishman LL, et al: Charcot pathogenesis: a study of in vivo gene expression. J Foot Ankle Surg 57: 1067, 2018.

  • 4

    Khan A, Petropoulos IN, Ponirakis G, et al: Corneal confocal microscopy detects severe small fiber neuropathy in diabetic patients with Charcot neuroarthropathy. J Diabetes Investig 9: 1167, 2018.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5

    Mooney V, Mankin HJ: A case of congenital insensitivity to pain with neuropathic arthropathy. Arthritis Rheum 9: 820, 1966.

  • 6

    Schwartzlow C, Kazamel M: Hereditary sensory and autonomic neuropathies: adding more to the classification. Curr Neurol Neurosci Rep 19: 52, 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7

    Mobini M, Javadzadeh A, Forghanizadeh J: Neuropathic osteoarthropathy in a patient with congenital insensitivity to pain. Arch Iran Med 12: 599, 2009.

    • Search Google Scholar
    • Export Citation
  • 8

    Gucev Z, Tasic V, Bogevska I, et al: Heterotopic ossifications and Charcot joints: congenital insensitivity to pain with anhidrosis (CIPA) and a novel NTRK1 gene mutation. Eur J Med Genet 63: 103613, 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9

    Kurth I: “Hereditary Sensory and Autonomic Neuropathy Type II,” in GeneReviews, edited by MP Adam, HH Ardinger, RA Pagon et al., Seattle, WA, University of Washington, Seattle, 1993.

    • Search Google Scholar
    • Export Citation
  • 10

    Nahorski MS, Chen YC, Woods CG: New mendelian disorders of painlessness. Trends Neurosci 38: 712, 2015.

  • 11

    Rahmani B, Fekrmandi F, Ahadi K, et al: A novel nonsense mutation in WNK1/HSN2 associated with sensory neuropathy and limb destruction in four siblings of a large Iranian pedigree. BMC Neurol 18: 195, 2018.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12

    Nicholson GA: “SPTLC1-Related Hereditary Sensory Neuropathy,” in GeneReviews, edited by MP Adam, HH Ardinger, RA Pagon et al., Seattle, WA, University of Washington, Seattle, 1993.

    • Search Google Scholar
    • Export Citation
  • 13

    Kornak U, Mademan I, Schinke M, et al: Sensory neuropathy with bone destruction due to a mutation in the membrane-shaping atlastin GTPase 3. Brain 137: 683, 2014.

  • 14

    Suriyanarayanan S, Auranen M, Toppila J, et al: The variant p.(Arg183Trp) in SPTLC2 causes late-onset hereditary sensory neuropathy. Neuromolecular Med 18: 81, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15

    Yuan J, Higuchi Y, Nagado T, et al: Novel mutation in the replication focus targeting sequence domain of DNMT1 causes hereditary sensory and autonomic neuropathy IE. J Peripher Nerv Syst 18: 89, 2013.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 16

    Nagasako EM, Oaklander AL, Dworkin RH: Congenital insensitivity to pain: an update. Pain 101: 213, 2003.

  • 17

    Drenth JP, Waxman SG: Mutations in sodium-channel gene SCN9A cause a spectrum of human genetic pain disorders. J Clin Invest 117: 3603, 2007.

  • 18

    Bennett DL, Woods CG: Painful and painless channelopathies. Lancet Neurol 13: 587, 2014.

  • 19

    McDermott LA, Weir GA, Themistocleous AC, et al: Defining the functional role of NaV1.7 in human nociception. Neuron 101: 905, 2019.

  • 20

    Hameed S: Nav1.7 and Nav1.8: role in the pathophysiology of pain. Mol Pain 15: 1744806919858801, 2019.

  • 21

    Majeed MH, Ubaidulhaq M, Rugnath A, et al: Extreme ends of pain sensitivity in SCN9A mutation variants: case report and literature review. Innov Clin Neurosci 15: 33, 2018.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 22

    Black JA, Waxman SG: Noncanonical roles of voltage-gated sodium channels. Neuron 80: 280, 2013.

  • 23

    Effraim PR, Huang J, Lampert A, et al: Fibroblast growth factor homologous factor 2 (FGF-13) associates with Nav1.7 in DRG neurons and alters its current properties in an isoform-dependent manner. Neurobiol Pain 6: 100029, 2019.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 24

    Cox JJ, Sheynin J, Shorer Z, et al: Congenital insensitivity to pain: novel SCN9A missense and in-frame deletion mutations. Hum Mutat 31: E1670, 2010.

  • 25

    Weiss J, Pyrski M, Jacobi E, et al: Loss-of-function mutations in sodium channel Nav1.7 cause anosmia. Nature 472: 186, 2011.

  • 26

    Doty RL, Shaman P, Dann M: Development of the University of Pennsylvania Smell Identification Test: a standardized microencapsulated test of olfactory function. Physiol Behav 32: 489, 1984.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 27

    Min JY, Min KB: Insulin resistance and the increased risk for smell dysfunction in US adults. Laryngoscope 128: 1992, 2018.

  • 28

    Phatarakijnirund V, Mumm S, McAlister WH, et al: Congenital insensitivity to pain: fracturing without apparent skeletal pathobiology caused by an autosomal dominant, second mutation in SCN11A encoding voltage-gated sodium channel 1.9. Bone 84: 289, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 29

    Schon K, Parker A, Woods CG: “Congenital Insensitivity to Pain Overview,” in GeneReviews, edited by MP Adam, HH Ardinger, RA Pagon et al., Seattle, WA, University of Washington, Seattle, 1993.

    • Search Google Scholar
    • Export Citation
  • 30

    Desiderio S, Vermeiren S, Van Campenhout C, et al: Prdm12 directs nociceptive sensory neuron development by regulating the expression of the NGF receptor TrkA. Cell Rep 26: 3522, 2019.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 31

    Zhang S, Sharif SM, Chen Y-C, et al: Clinical features for diagnosis and management of patients with PRDM12 congenital insensitivity to pain. J Med Genet 53: 533, 2016.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 32

    Woods CG, Babiker MO, Horrocks I, et al: The phenotype of congenital insensitivity to pain due to the NaV1.9 variant p.L811P. Eur J Hum Genet 23: 561, 2015.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33

    Duan G, Guo S, Zhang Y, et al: The effect of SCN9A variation on basal pain sensitivity in the general population: an experimental study in young women. J Pain 16: 971, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 34

    Wadhawan S, Pant S, Golhar R, et al: NaV channel variants in patients with painful and nonpainful peripheral neuropathy. Neurol Genet 3: e207, 2017.

The Association of Olfactory Impairment with Charcot Neuroarthropathy and Possible Links to Causation

Andrew J. RaderIndiana Foot & Ankle, Jasper, IN

Search for other papers by Andrew J. Rader in
Current site
Google Scholar
PubMed
Close
 DPM
and
Aaron RuterLakeshore Bone and Joint Institute, Crown Point, IN.
Indiana Foot & Ankle, Jasper, IN

Search for other papers by Aaron Ruter in
Current site
Google Scholar
PubMed
Close
 DPM
Restricted access

Background: Charcot neuroarthropathy (CN) is a devastating complication of some diseases affecting the peripheral nervous system. Initial subjective and objective presentation of the disease can be variable. Common among all presentations seems to be uncontrolled inflammation yielding dislocations and/or fractures. The exact cause remains the subject of much debate.

Methods: Our study retrospectively looks at the function of olfactory function in consecutive patients with CN and compares the findings with a nonaffected population. The University of Pennsylvania Smell Identification Test was used to assess olfaction and document microsomia.

Results: Twenty consecutive patients presenting with CN demonstrated significant (P < .0001) microsomia when compared to an unaffected population with diabetes.

Conclusions: Microsomia is strongly associated with CN. This finding may be correlated to voltage-gated sodium 1.7 channel impairment and appears to be a candidate precursor for the development of CN.

Corresponding author: Andrew J Rader, DPM, Indiana Foot & Ankle, 645 W 5th St, Jasper, IN 47546. (E-mail: drajrader@gmail.com)