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. 2019 Mar;90(3):342-352.
doi: 10.1136/jnnp-2018-319042. Epub 2018 Dec 15.

Yield of peripheral sodium channels gene screening in pure small fibre neuropathy

Ivo Eijkenboom #  1   2 , Maurice Sopacua #  2   3 , Janneke G J Hoeijmakers  2   3 , Bianca T A de Greef  2   3 , Patrick Lindsey  1 , Rowida Almomani  1   2   4 , Margherita Marchi  5 , Jo Vanoevelen  1 , Hubertus J M Smeets  1   2 , Stephen G Waxman  6   7 , Giuseppe Lauria  5   8 , Ingemar S J Merkies  2   9 , Catharina G Faber  2   3 , Monique M Gerrits  10
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Free article

Yield of peripheral sodium channels gene screening in pure small fibre neuropathy

Ivo Eijkenboom et al. J Neurol Neurosurg Psychiatry. 2019 Mar.
Free article

Abstract

Background: Neuropathic pain is common in peripheral neuropathy. Recent genetic studies have linked pathogenic voltage-gated sodium channel (VGSC) variants to human pain disorders. Our aims are to determine the frequency of SCN9A, SCN10A and SCN11A variants in patients with pure small fibre neuropathy (SFN), analyse their clinical features and provide a rationale for genetic screening.

Methods: Between September 2009 and January 2017, 1139 patients diagnosed with pure SFN at our reference centre were screened for SCN9A, SCN10A and SCN11A variants. Pathogenicity of variants was classified according to established guidelines of the Association for Clinical Genetic Science and frequencies were determined. Patients with SFN were grouped according to the VGSC variants detected, and clinical features were compared.

Results: Among 1139 patients with SFN, 132 (11.6%) patients harboured 73 different (potentially) pathogenic VGSC variants, of which 50 were novel and 22 were found in ≥ 1 patient. The frequency of (potentially) pathogenic variants was 5.1% (n=58/1139) for SCN9A, 3.7% (n=42/1139) for SCN10A and 2.9% (n=33/1139) for SCN11A. Only erythromelalgia-like symptoms and warmth-induced pain were significantly more common in patients harbouring VGSC variants.

Conclusion: (Potentially) pathogenic VGSC variants are present in 11.6% of patients with pure SFN. Therefore, genetic screening of SCN9A, SCN10A and SCN11A should be considered in patients with pure SFN, independently of clinical features or underlying conditions.

Keywords: SCN10A; SCN11A; SCN9A; frequency of (potentially) pathogenic variants; neuropathic pain; painful neuropathy; small fibre neuropathy; voltage-gated sodium channels.

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Conflict of interest statement

Competing interests: JGJH reports personal fees from Pfizer Inc. (travel funding and speakers’ honorarium) and grants from Prinses Beatrix Spierfonds (W.OK17-09), outside the submitted work. SGW reports grants from European Union’s Horizon 2020 research and innovation programme Marie Sklodowska-Curie grant for PAIN-Net, Molecule-to-man pain network (grant no. 721841) and European Union 7th Framework Programme (grant no. 602273) for the PROPANE study and was supported in part by the Rehabilitation Research and Development Service and Biomedical Laboratory Research Service, Department of Veterans Affairs, outside the submitted work. GL reports grants from European Union’s Horizon 2020 research and innovation programme Marie Sklodowska-Curie grant for PAIN-Net, Molecule-to-man pain network (grant no. 721841) and European Union 7th Framework Programme (grant n°602273) for the PROPANE study and participates in Steering committees/advisory boards for studies in small fibre neuropathy of Biogen/Convergence, Vertex and Chromocell, outside the submitted work. ISJM reports grants from Talecris Talents program, GSB CIDP Foundation International, Prinses Beatrix Spierfonds (W.OR12-01, W.OR15-25) and European Union 7th Framework Programme (grant no. 602273), participates Steering committees of the Talecris ICE Study, LFB, CSL Behring, Novartis, Grifols and Octapharma, serves on the editorial board of the Journal of Peripheral Nervous system and is a member of the Inflammatory Neuropathy Consortium (INC) and Peripheral Nerve Society, outside the submitted work. CGF reports grants from European Union’s Horizon 2020 research and innovation programme Marie Sklodowska-Curie grant for PAIN-Net, Molecule-to-man pain network (grant no. 721841), European Union 7th Framework Programme (grant n°602273) for the PROPANE study, Prinses Beatrix Spierfonds (W.OR12-01, W.OR15-25), Grifols and Lamepro for a trial on IVIg in small fibre neuropathy and participates in Steering committees/advisory boards for studies in small fibre neuropathy of Biogen/Convergence, Vertex and Chromocell, outside the submitted work. Other authors have no conflicts of interests to declare.

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