{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T15:09:12Z","timestamp":1784214552876,"version":"3.55.0"},"reference-count":23,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T00:00:00Z","timestamp":1718928000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Health Labour Sciences Research Grant","award":["22FC1006"],"award-info":[{"award-number":["22FC1006"]}]},{"name":"Health Labour Sciences Research Grant","award":["045"],"award-info":[{"award-number":["045"]}]},{"name":"Japan Agency for Medical Research and Development","award":["22FC1006"],"award-info":[{"award-number":["22FC1006"]}]},{"name":"Japan Agency for Medical Research and Development","award":["045"],"award-info":[{"award-number":["045"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms25136832","type":"journal-article","created":{"date-parts":[[2024,6,21]],"date-time":"2024-06-21T08:50:08Z","timestamp":1718959808000},"page":"6832","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Genetic Analysis of SCN11A, SCN10A, and SCN9A in Familial Episodic Pain Syndrome (FEPS) in Japan and Proposal of Clinical Diagnostic Criteria"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5627-4217","authenticated-orcid":false,"given":"Atsuko","family":"Noguchi","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4762-8578","authenticated-orcid":false,"given":"Tohru","family":"Tezuka","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacogenetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"},{"name":"Laboratory of Integrative Molecular Medicine, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2456-9512","authenticated-orcid":false,"given":"Hiroko","family":"Okuda","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacogenetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"},{"name":"Department of Preventive Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5664-6869","authenticated-orcid":false,"given":"Hatasu","family":"Kobayashi","sequence":"additional","affiliation":[{"name":"Department of Environmental and Molecular Medicine, Mie University Graduate School of Medicine, Edobashi 2-174, Tsu 514-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7319-123X","authenticated-orcid":false,"given":"Kouji H.","family":"Harada","sequence":"additional","affiliation":[{"name":"Department of Health and Environmental Sciences, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0992-064X","authenticated-orcid":false,"given":"Takeshi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho, Sakyo-ku, Kyoto 606-8507, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9017-3842","authenticated-orcid":false,"given":"Shinji","family":"Akioka","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5467-8592","authenticated-orcid":false,"given":"Keiko","family":"Wada","sequence":"additional","affiliation":[{"name":"Department of Epidemiology and Preventive Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2644-8383","authenticated-orcid":false,"given":"Aya","family":"Takeya","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacogenetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"},{"name":"Department of Gynecology, Kyoto Okamoto Memorial Hospital, 100 Sayamanishi-No-Kuchi, Kumiyama-cho, Kuse-gun, Kyoto 613-0034, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Risako","family":"Kabata-Murasawa","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Iwate Prefectural Nanko Hospital, 17 Ohira, Kitsunezenji, Ichinoseki-shi 027-0031, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1385-3985","authenticated-orcid":false,"given":"Daiki","family":"Kondo","sequence":"additional","affiliation":[{"name":"Devision of Pediatrics, Akita Kousei Medical Center, 1-1-1 Iijima Nishibukuro, Akita 011-0948, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7585-1182","authenticated-orcid":false,"given":"Ken","family":"Ishikawa","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Iwate Medical University, 1-1 Iidai-dori 2-Chome, Yahaba-cho, Shiwa-gun 028-3695, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3275-1979","authenticated-orcid":false,"given":"Takeshi","family":"Asano","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Nippon Medical School Chiba Hokusoh Hospital, 1715 Kamagari, Inzai 270-1694, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2962-8630","authenticated-orcid":false,"given":"Michimasa","family":"Fujiwara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, NHO Fukuyama Medical Center, 14-17, 4-Chome, Okinogami-cho, Fukuyama City 720-8520, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2021-7541","authenticated-orcid":false,"given":"Nozomi","family":"Hishikawa","sequence":"additional","affiliation":[{"name":"Department of Neurology, Kurashiki Heisei Hospital, 4-3-38 Oimatsu-cho, Kurashiki City 710-0826, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2508-2810","authenticated-orcid":false,"given":"Tomoyuki","family":"Mizukami","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, National Hospital Organization Kumamoto Medical Center, 1-5 Ninomaru, Chuo-ku, Kumamoto 860-0008, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2267-1940","authenticated-orcid":false,"given":"Toshiaki","family":"Hitomi","sequence":"additional","affiliation":[{"name":"Department of Preventive Medicine, St. Marianna University School of Medicine, 2-16-1, Sugao, Miyamae-ku, Kawasaki 216-8511, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-4096-8677","authenticated-orcid":false,"given":"Shohab","family":"Youssefian","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacogenetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"},{"name":"Laboratory of Molecular Biosciences, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4457-7458","authenticated-orcid":false,"given":"Yoshihiro","family":"Nagai","sequence":"additional","affiliation":[{"name":"Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1765-0088","authenticated-orcid":false,"given":"Manabu","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Division of General Pediatrics, Saitama Prefectural Children\u2019s Medical Center, 1-2 Shin-Toshin, Chuo-ku, Saitama 330-8777, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8825-2717","authenticated-orcid":false,"given":"Kaoru","family":"Eto","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Tokyo Women\u2019s Medical University, 8-1 Kawada-cho, Shinjuku-ku, Tokyo 162-8666, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4199-0728","authenticated-orcid":false,"given":"Hideaki","family":"Shiraishi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Hokkaido University Hospital, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-0845","authenticated-orcid":false,"given":"Fumimasa","family":"Amaya","sequence":"additional","affiliation":[{"name":"Department of Pain Management and Palliative Care Medicine, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1937-3176","authenticated-orcid":false,"given":"Akio","family":"Koizumi","sequence":"additional","affiliation":[{"name":"Department of Pain Pharmacogenetics, Graduate School of Medicine, Kyoto University, Yoshida Konoe-cho, Sakyo-ku, Kyoto 606-8501, Japan"},{"name":"Institute of Public Health and Welfare Research, 18-13 Uzumasa Tanamoricho, Ukyo-ku, Kyoto 616-8141, 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