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Neurological Sciences
Published in: Neurological Sciences 9/2022

07-05-2022 | Pain Syndromes | Original Article

Pathological changes of the sural nerve in patients with familial episodic pain syndrome

Authors: Yilei Zheng, Pengcheng Huang, Shumeng Li, Kaiyan Jiang, Binbin Zhou, Xin Fang, Meihong Zhou, Daojun Hong, Min Zhu

Published in: Neurological Sciences | Issue 9/2022

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Abstract

Background

Familial episodic pain syndrome type 3 (FEPS3) is an inherited disorder characterized by the early-childhood onset of severe episodic pain that primarily affects the distal extremities. As skin biopsy has revealed a reduction in intraepidermal nerve fiber density and degeneration of the unmyelinated axons, it remains unclear whether FEPS3 patients have pathological changes in the peripheral nerve.

Methods

The clinical features of patients with FEPS3 were summarized in a large autosomal dominant family. Sural nerve biopsies were conducted in two patients. Whole exome sequencing (WES) was performed in the index patient. Sanger sequencing was used to analyze family co-segregation.

Results

Fourteen members exhibited typical and uniform clinical phenotypes characterized by length-dependent and age-dependent severe episodic pain affecting the distal extremities, which can be relieved with anti-inflammatory medicine. The WES revealed a heterozygous mutation c.665G > A (p.R222H) in the SCN11A gene, which was co-segregated with the clinical phenotype in this family. A sural biopsy in patient V:1, who was experiencing episodic pain at 16 years old, showed normal structure, while the sural nerve in patient IV:1, whose pain attack had completely diminished at 42 years old, displayed a decrease of the density of unmyelinated axons with the axonal degeneration.

Conclusions

The clinical phenotype of FEPS3 showed distinctive characteristics that likely arise from dysfunctional nociceptive neurons that lack detectable pathological alterations in the nerve fibers. Nevertheless, long-term dysfunction of the Nav1.9 channel may cause degeneration of the unmyelinated fibers in FEPS3 patient with pain remission.
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Metadata
Title
Pathological changes of the sural nerve in patients with familial episodic pain syndrome
Authors
Yilei Zheng
Pengcheng Huang
Shumeng Li
Kaiyan Jiang
Binbin Zhou
Xin Fang
Meihong Zhou
Daojun Hong
Min Zhu
Publication date
07-05-2022
Publisher
Springer International Publishing
Keyword
Pain Syndromes
Published in
Neurological Sciences / Issue 9/2022
Print ISSN: 1590-1874
Electronic ISSN: 1590-3478
DOI
https://doi.org/10.1007/s10072-022-06107-7

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