title: At-risk phenotype of neurofibromatose-1 patients: a multicentre case-control study.
abstract: OBJECTIVE
  To assess associations between subcutaneous neurofibromas (SC-NFs) and internal neurofibromas in patients with neurofibromatosis type 1 (NF-1) and to determine whether the association between SC-NFs and peripheral neuropathy was ascribable to internal neurofibromas.
  
  
  METHODS
  Prospective multicentre case-control study. Between 2005 and 2008, 110 NF-1 adults having two or more SC-NFs were individually matched for age, sex and hospital with 110 controls who had no SC-NF. Patients underwent standardized MRI of the spinal cord, nerve roots and sciatic nerves and an electrophysiological study. Analyses used adjusted multinomial logistic regression (ORa) to estimate the risk of the presence of internal neurofibromas or peripheral neuropathies associated with patients presented 2 to 9 SC-NFs, at least 10 SC-NFs as compared to patients without any (referential category).
  
  
  RESULTS
  Cases had a mean age of 41 (± 13) years; 85 (80%) had two to nine SC-NFs and 21 (19%) at least ten SC-NFs. SC-NFs were more strongly associated with internal neurofibromas in patients with ten or more SC-NFs than in patients with fewer NF-SCs (e.g., sciatic nerve, aOR = 29.1 [8.5 to 100] vs. 4.3 [2.1 to 9.0]). The association with SC-NFs was stronger for diffuse, intradural, and > 3 cm internal neurofibromas than with other internal neurofibromas. Axonal neuropathy with slowed conduction velocities (SCV) was more strongly associated with having at least ten SC-NFs (aOR = 29.9, 5.5 to 162.3) than with having fewer SC-NFs (aOR = 4.4, 0.9 to 22.0). Bivariate analyses showed that the association between axonal neuropathy with SCV and sciatic neurofibromas was mediated by the association between SC-NFs and sciatic neurofibromas.
  
  
  CONCLUSIONS
  The at-risk phenotype of NF-1 patients (i.e. NF-1 patients with SC-NFs) is ascribable to associations linking SC-NFs to internal neurofibromas at risk for malignant transformation and to axonal neuropathies with slowed conduction velocities. Axonal neuropathies with SCV are particularly common in patients with at least ten SC-NFs.
authors.affiliation: Université Paris Est (UPEC), LIC EA4393 (Laboratoire d'Investigation Clinique), F-94010 Créteil, France.
authors.forename: Emilie
authors.initials: E
authors.lastname: Sbidian
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bastuji-Garin
authors.forename: Laurence
authors.initials: L
authors.lastname: Valeyrie-Allanore
authors.forename: Salah
authors.initials: S
authors.lastname: Ferkal
authors.forename: Jean P
authors.initials: JP
authors.lastname: Lefaucheur
authors.forename: Alain
authors.initials: A
authors.lastname: Drouet
authors.forename: Pierre
authors.initials: P
authors.lastname: Brugière
authors.forename: Cédric
authors.initials: C
authors.lastname: Vialette
authors.forename: Patrick
authors.initials: P
authors.lastname: Combemale
authors.forename: Sébastien
authors.initials: S
authors.lastname: Barbarot
authors.forename: Pierre
authors.initials: P
authors.lastname: Wolkenstein
mesh_terms: D000328:Adult; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009455:Neurofibroma / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D009456:Neurofibromatosis 1 / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D010523:Peripheral Nervous System Diseases / Q000209:etiology*; D010641:Phenotype; D011446:Prospective Studies; D011859:Radiography; D012878:Skin Neoplasms / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D040521:Subcutaneous Tissue / Q000000981:diagnostic imaging / Q000473:pathology*