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Neurofibromatous neuropathy in neurofibromatosis 1 (NF1)
  1. R E Ferner1,
  2. R A C Hughes1,
  3. S M Hall2,
  4. M Upadhyaya3,
  5. M R Johnson4
  1. 1Department of Clinical Neurosciences, Guy’s, Kings and St. Thomas’ School of Medicine, London, UK
  2. 2Centre for Neuroscience Research, Guy’s, Kings and St. Thomas’ School of Biomedical Sciences, London, UK
  3. 3Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK
  4. 4Division of Neurosciences, Charing Cross Hospital, London, UK
  1. Correspondence to:
 Dr Rosalie E Ferner
 Department of Clinical Neurosciences, 2nd floor Hodgkin Building, Guy’s, King’s and St. Thomas’ School of Medicine, London Bridge, London SE1 1UL, UK; rosalie.fernerkcl.ac.uk

Abstract

Background: Neurofibromatosis 1 (NF1) is a common, autosomal dominant, neurocutaneous disease that is clinically and genetically distinct from the rare condition neurofibromatosis 2 (NF2). Neurofibromatous neuropathy has been regarded as a common feature of NF2, but is an unusual and unexplained complication of NF1. The clinical and histological features of the NF1 neuropathy are distinct from those encountered in NF2. We describe eight patients with a symmetrical polyneuropathy, which has been called neurofibromatous neuropathy

Methods: Clinical assessments, laboratory investigations, neuroimaging, and neurophysiology were undertaken in eight individuals with neurofibromatous neuropathy. None were referred because of neuropathic symptoms. Two subjects underwent sural nerve biopsy and three agreed to mutational analysis.

Results: The patients had an indolent symmetrical predominantly sensory axonal neuropathy and unusually early development of large numbers of neurofibromas. The biopsied nerves showed diffuse neurofibromatous change and disruption of the perineurium. Two patients developed a high grade malignant peripheral nerve sheath tumour. Disease causing mutations were detected in two individuals and molecular studies did not reveal any whole gene deletions.

Conclusions: Neurofibromatous neuropathy occurred in 1.3% of 600 patients with NF1. Its cause may be a diffuse neuropathic process arising from inappropriate signalling between Schwann cells, fibroblasts, and perineurial cells.

  • GRD, guanosine triphosphatase related domain
  • MPNST, malignant peripheral nerve sheath tumour
  • NF1, neurofibromatosis 1
  • NF2, neurofibromatosis 1
  • neurofibroma
  • neurofibromatosis 1
  • neuropathy

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Footnotes

  • Conflict of interest: none declared.