RT Journal Article SR Electronic T1 Neurofibromatous neuropathy in neurofibromatosis 1 (NF1) JF Journal of Medical Genetics JO J Med Genet FD BMJ Publishing Group Ltd SP 837 OP 841 DO 10.1136/jmg.2004.021683 VO 41 IS 11 A1 Ferner, R E A1 Hughes, R A C A1 Hall, S M A1 Upadhyaya, M A1 Johnson, M R YR 2004 UL http://jmg.bmj.com/content/41/11/837.abstract AB 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.