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Multicenter Study
. 2011 Jul 13:6:51.
doi: 10.1186/1750-1172-6-51.

At-risk phenotype of neurofibromatose-1 patients: a multicentre case-control study

Emilie Sbidian  1 , Sylvie Bastuji-Garin, Laurence Valeyrie-Allanore, Salah Ferkal, Jean P Lefaucheur, Alain Drouet, Pierre Brugière, Cédric Vialette, Patrick Combemale, Sébastien Barbarot, Pierre Wolkenstein; NF France Network
Collaborators, Affiliations
Multicenter Study

At-risk phenotype of neurofibromatose-1 patients: a multicentre case-control study

Emilie Sbidian et al. Orphanet J Rare Dis. .

Abstract

Objectives: 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.

Patients and 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.

Conclusion: 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.

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Figures

Figure 1
Figure 1
Odds ratios (ORs) with their 95% confidence intervals for several types of internal neurofibromas and peripheral neuropathies in patients with two to nine subcutaneous neurofibromas (SC-NFs) or at least ten SC-NFs. The ORs associated with each type of internal neurofibroma and peripheral neuropathy were estimated using multinomial logistic regression adjusted for the matching variables (age, sex, and centre), using the control group of patients with neurofibromatosis type 1 and no SC-NFs (n = 102) as the reference category. ORs were log-transformed.
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References

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