Abstract：
Voltage-gated sodium channels are essential for the generation and conduction of electrical impulses in excitable cells. Sodium channel Nav 1.7, encoded by the SCN9A-gene, has been of special interest in the last decades because missense gain-of-function mutations have been linked to a spectrum of neuropathic pain conditions, including inherited erythermalgia (IEM), paroxysmal extreme pain disorder (PEPD), and small fiber neuropathy (SFN).
In this case report, we present a 61-year-old woman who was referred to our tertiary referral center in a standard day care setting with suspicion of SFN. We performed additional investigations: skin biopsy to determine the intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST), and blood examination (including DNA analysis) for possible underlying conditions.
The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G > A in the SCN9A-gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. Because its pathogenicity has never been functionally confirmed, the variant is classified as a variance of unknown significance (VUS)/risk factor. This suggests that another genetic and/or environmental substrate plays a role in the development of neuropathic conditions like described.
We have described this as the SCN9A-pain triangle phenomenon. Treatment should focus on pain management, genetic counseling, and improving/maintaining quality of life by treating symptoms and, if indicated, starting a rehabilitation program.
In this case report, we present a 61-year-old woman who was referred to our tertiary referral center in a standard day care setting with suspicion of SFN. We performed additional investigations: skin biopsy to determine the intra-epidermal nerve fiber density (IENFD), quantitative sensory testing (QST), and blood examination (including DNA analysis) for possible underlying conditions.
The patient showed a clinical picture that fulfilled the criteria of IEM, PEPD, and SFN. DNA analysis revealed the heterozygous variant c.554G > A in the SCN9A-gene (OMIM 603415). This variant has already been described in all three human pain conditions separately, but never in one patient having symptoms of all three conditions. Because its pathogenicity has never been functionally confirmed, the variant is classified as a variance of unknown significance (VUS)/risk factor. This suggests that another genetic and/or environmental substrate plays a role in the development of neuropathic conditions like described.
We have described this as the SCN9A-pain triangle phenomenon. Treatment should focus on pain management, genetic counseling, and improving/maintaining quality of life by treating symptoms and, if indicated, starting a rehabilitation program.
摘要：
电压门控钠通道对于可兴奋细胞中电脉冲的产生和传导至关重要。钠通道Nav1.7，由SCN9A基因编码，在过去的几十年中，人们特别感兴趣，因为错义功能获得突变与一系列神经性疼痛疾病有关，包括遗传性红斑狼疮（IEM），阵发性极度疼痛障碍（PEPD），和小纤维神经病变(SFN)。
在这种情况下，我们介绍了一名61岁的女性,她在标准日托环境中被转诊到我们的三级转诊中心,怀疑有SFN.我们进行了额外的调查：皮肤活检以确定表皮内神经纤维密度（IENFD），定量感官测试(QST)，和血液检查（包括DNA分析）可能的潜在条件。
患者的临床表现符合IEM的标准，PEPD,和SFN。DNA分析揭示了SCN9A基因中的杂合变体c.554G>A(OMIM603415)。这种变体已经在所有三种人类疼痛状况中单独描述过，但从来没有一个病人有所有三种情况的症状。因为它的致病性从未在功能上得到证实，该变异被分类为未知显著性变异(VUS)/危险因素.这表明另一种遗传和/或环境底物在如所述的神经性病症的发展中起作用。
我们已经将其描述为SCN9A-疼痛三角现象。治疗应侧重于疼痛管理，遗传咨询,并通过治疗症状改善/维持生活质量，如果指示，开始一个康复计划。
在这种情况下，我们介绍了一名61岁的女性,她在标准日托环境中被转诊到我们的三级转诊中心,怀疑有SFN.我们进行了额外的调查：皮肤活检以确定表皮内神经纤维密度（IENFD），定量感官测试(QST)，和血液检查（包括DNA分析）可能的潜在条件。
患者的临床表现符合IEM的标准，PEPD,和SFN。DNA分析揭示了SCN9A基因中的杂合变体c.554G>A(OMIM603415)。这种变体已经在所有三种人类疼痛状况中单独描述过，但从来没有一个病人有所有三种情况的症状。因为它的致病性从未在功能上得到证实，该变异被分类为未知显著性变异(VUS)/危险因素.这表明另一种遗传和/或环境底物在如所述的神经性病症的发展中起作用。
我们已经将其描述为SCN9A-疼痛三角现象。治疗应侧重于疼痛管理，遗传咨询,并通过治疗症状改善/维持生活质量，如果指示，开始一个康复计划。
