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

Ivo Eijkenboom, Maurice Sopacua, Janneke G.J. Hoeijmakers, Bianca T.A. De Greef, Patrick Lindsey, Rowida Almomani, Margherita Marchi, Jo Vanoevelen, Hubertus J.M. Smeets, Stephen G. Waxman, Giuseppe Lauria, Ingemar S.J. Merkies, Catharina G. Faber, Monique M. Gerrits

Research output: Contribution to journalArticle

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.

Original languageEnglish
JournalJournal of Neurology, Neurosurgery and Psychiatry
DOIs
Publication statusAccepted/In press - Jan 1 2018

Fingerprint

Sodium Channels
Voltage-Gated Sodium Channels
Genes
Genetic Testing
Erythromelalgia
Small Fiber Neuropathy
Somatoform Disorders
Neuralgia
Peripheral Nervous System Diseases
Virulence
Guidelines
Pain

Keywords

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

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology
  • Psychiatry and Mental health

Cite this

Eijkenboom, I., Sopacua, M., Hoeijmakers, J. G. J., De Greef, B. T. A., Lindsey, P., Almomani, R., ... Gerrits, M. M. (Accepted/In press). Yield of peripheral sodium channels gene screening in pure small fibre neuropathy. Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2018-319042

Yield of peripheral sodium channels gene screening in pure small fibre neuropathy. / Eijkenboom, Ivo; Sopacua, Maurice; Hoeijmakers, Janneke G.J.; De Greef, Bianca T.A.; Lindsey, Patrick; Almomani, Rowida; Marchi, Margherita; Vanoevelen, Jo; Smeets, Hubertus J.M.; Waxman, Stephen G.; Lauria, Giuseppe; Merkies, Ingemar S.J.; Faber, Catharina G.; Gerrits, Monique M.

In: Journal of Neurology, Neurosurgery and Psychiatry, 01.01.2018.

Research output: Contribution to journalArticle

Eijkenboom, I, Sopacua, M, Hoeijmakers, JGJ, De Greef, BTA, Lindsey, P, Almomani, R, Marchi, M, Vanoevelen, J, Smeets, HJM, Waxman, SG, Lauria, G, Merkies, ISJ, Faber, CG & Gerrits, MM 2018, 'Yield of peripheral sodium channels gene screening in pure small fibre neuropathy', Journal of Neurology, Neurosurgery and Psychiatry. https://doi.org/10.1136/jnnp-2018-319042
Eijkenboom, Ivo ; Sopacua, Maurice ; Hoeijmakers, Janneke G.J. ; De Greef, Bianca T.A. ; Lindsey, Patrick ; Almomani, Rowida ; Marchi, Margherita ; Vanoevelen, Jo ; Smeets, Hubertus J.M. ; Waxman, Stephen G. ; Lauria, Giuseppe ; Merkies, Ingemar S.J. ; Faber, Catharina G. ; Gerrits, Monique M. / Yield of peripheral sodium channels gene screening in pure small fibre neuropathy. In: Journal of Neurology, Neurosurgery and Psychiatry. 2018.
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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.",
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AU - Eijkenboom, Ivo

AU - Sopacua, Maurice

AU - Hoeijmakers, Janneke G.J.

AU - De Greef, Bianca T.A.

AU - Lindsey, Patrick

AU - Almomani, Rowida

AU - Marchi, Margherita

AU - Vanoevelen, Jo

AU - Smeets, Hubertus J.M.

AU - Waxman, Stephen G.

AU - Lauria, Giuseppe

AU - Merkies, Ingemar S.J.

AU - Faber, Catharina G.

AU - Gerrits, Monique M.

PY - 2018/1/1

Y1 - 2018/1/1

N2 - 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.

AB - 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.

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