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Updated: Jun 27, 2025
Targeted Next-generation Sequencing and Bioinformatics Pipeline to Evaluate Genetic Determinants of Constitutional Disease
Published on: April 4, 2018
[Sequence variants of unknown significance in small fiber neuropathy : Characterization of a heterogeneous patient
Caren Meyer Zu Altenschildesche1, Nadine Egenolf1, Annette Lischka2
1Neurologische Klinik des Universitätsklinikums Würzburg, Josef-Schneider-Str. 11, 97080, Würzburg, Deutschland.
Background:
In almost half of patients suffering from small fiber neuropathies (SFN), the etiology remains elusive. For these patients with "idiopathic SFN", symptomatic analgesic therapy is the only option. Reports on a potential genetic background of neuropathic pain syndromes are increasing and particularly in SFN patients, several genetic variants were found mainly located in genes encoding voltage-gated sodium channels. Although up to 30% of SFN patients show genetic alterations, most of these remain of "unknown pathogenic significance" and little is known about "genetic SFN".
Objectives:
The study aimed to determine clinical characteristics of SFN patients carrying a rare genetic variant of unknown significance in pain-associated genes.
Materials And Methods:
From 2015 to 2020, 66 patients with primarily idiopathic SFN were examined and rare gene variants of unknown significance detected in 13/66 (20%) of these. A detailed medical history with focus on pain was recorded and patients filled in standardized questionnaires to assess physical and emotional burden due to pain.
Results:
The authors found 13/66 (20%) patients with rare variants of unknown significance located in pain-associated genes who reported pain refractory to analgesic treatment, a higher number of external factors influencing clinical symptoms, and a higher level of physical impairment and emotional stress due to pain compared with patients without such genetic variants.
Conclusions:
Early genetic assessment is recommended to optimize the management of patients with potentially hereditary SFN. Early access to rehabilitation and mental support as well as a consequent elimination of external triggering factors should be granted.
