家族性发作性疼痛综合征(FEPS)是一种儿童早期发作的严重发作性肢体疼痛疾病,主要由SCN11A的致病变体引起,SCN10A,SCN9A,它们编码三个电压门控钠通道(VGSCs),在初级感觉神经元中表达为伤害感受器兴奋性的关键决定因素。可能仍有许多未确诊的FEPS患者。更好地理解相关的发病机制,流行病学,和临床特征需要提供适当的诊断和护理。对于这项研究,在全国范围内招募日本患者是使用临时临床诊断标准进行的,其次是SCN11A基因检测,SCN10A,SCN9A在招募的212名患者中,基因检测显示,64名患者(30.2%)携带这些基因的致病性或可能的致病性变异,由42(19.8%)组成,14(6.60%),和8例(3.77%)患有SCN11A变异的患者,SCN10A,SCN9A,分别。同时,符合暂定临床标准的患者比例为89.1%,52.0%,在具有三个基因中的每一个的致病性或可能致病性变异的患者中,有54.5%,表明这些临床标准的有效性,特别是SCN11A变异的患者。FEPS的这些临床诊断标准将加速在日本意外流行的具有潜在致病变异的患者的招募。
Familial episodic pain syndrome (FEPS) is an early childhood onset disorder of severe episodic limb pain caused mainly by pathogenic variants of
SCN11A, SCN10A, and SCN9A, which encode three voltage-gated sodium channels (VGSCs) expressed as key determinants of nociceptor excitability in primary sensory neurons. There may still be many undiagnosed patients with FEPS. A better understanding of the associated pathogenesis, epidemiology, and clinical characteristics is needed to provide appropriate diagnosis and care. For this study, nationwide recruitment of Japanese patients was conducted using provisional clinical diagnostic criteria, followed by genetic testing for
SCN11A, SCN10A, and SCN9A. In the cohort of 212 recruited patients, genetic testing revealed that 64 patients (30.2%) harbored pathogenic or likely pathogenic variants of these genes, consisting of 42 (19.8%), 14 (6.60%), and 8 (3.77%) patients with variants of
SCN11A, SCN10A, and SCN9A, respectively. Meanwhile, the proportions of patients meeting the tentative clinical criteria were 89.1%, 52.0%, and 54.5% among patients with pathogenic or likely pathogenic variants of each of the three genes, suggesting the validity of these clinical criteria, especially for patients with
SCN11A variants. These clinical diagnostic criteria of FEPS will accelerate the recruitment of patients with underlying pathogenic variants who are unexpectedly prevalent in Japan.