{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T06:11:28Z","timestamp":1779257488895,"version":"3.51.4"},"reference-count":16,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pediatr."],"abstract":"<jats:p>\n                    Congenital insensitivity to pain with anhidrosis (CIPA) is an extremely rare autosomal recessive disorder. Its core clinical manifestations include profound pain insensitivity, generalized anhidrosis, and subsequent recurrent hyperthermia. To date, only a few hundred cases have been reported in the literature. An 8-month-old female infant was admitted with a 14-day history of recurrent fever that was unresponsive to systemic antimicrobial therapy. Dynamic clinical monitoring revealed an environment-dependent body temperature. Physical examination showed dry and coarse palms, accompanied by painless oral ulcers and painless distal finger injuries. Retrospective history taking confirmed a lack of sweating during febrile episodes and an absence of pain perception. Whole-exome and Sanger sequencing identified compound heterozygous variants in the\n                    <jats:italic>NTRK1<\/jats:italic>\n                    gene, comprising a maternal intronic variant (c.851-33T\u2009&amp;gt;\u2009A) and a paternal large deletion at 1q23.1 encompassing exons 5\u20137. A definitive clinical diagnosis of CIPA was established. In infants presenting with refractory fever, clinicians should maintain a high index of suspicion for non-infectious etiologies. Early evaluation for anhidrosis and pain insensitivity, along with the inclusion of CIPA in the differential diagnosis, can expedite definitive diagnosis, prevent secondary injuries, and facilitate timely genetic counseling.\n                  <\/jats:p>","DOI":"10.3389\/fped.2026.1844909","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:47:09Z","timestamp":1779256029000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Early clinical diagnosis of congenital insensitivity to pain with anhidrosis in an infant: a case report"],"prefix":"10.3389","volume":"14","author":[{"given":"Ziqing","family":"Tang","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]},{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fenfen","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piaopiao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyu","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hongyang","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medical University","place":["Weifang, Shandong, China"]},{"name":"Department of Pediatrics, Jinan Central Hospital","place":["Jinan, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e36955","DOI":"10.1097\/MD.0000000000036955","article-title":"Phenotypes of a toddler with hereditary sensory and autonomic neuropathy type IV: comparing with normal: a case report","volume":"103","author":"Xu","year":"2024","journal-title":"Medicine (Baltimore)"},{"key":"B2","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1007\/s004399900205","article-title":"Mutation and polymorphism analysis of the TRKA (NTRK1) gene encoding a high-affinity receptor for nerve growth factor in congenital insensitivity to pain with anhidrosis (CIPA) families","volume":"106","author":"Miura","year":"2000","journal-title":"Hum Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1177\/0300060517747164","article-title":"Phenotypic heterogeneity of intellectual disability in patients with congenital insensitivity to pain with anhidrosis: a case report and literature review","volume":"46","author":"Liu","year":"2018","journal-title":"J Int Med Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1016\/j.cell.2018.12.015","article-title":"Predicting splicing from primary sequence with deep learning","volume":"176","author":"Jaganathan","year":"2019","journal-title":"Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"D948","DOI":"10.1093\/nar\/gkae1071","article-title":"Ensembl 2025","volume":"53","author":"Dyer","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B6","doi-asserted-by":"publisher","first-page":"D609","DOI":"10.1093\/nar\/gkae1010","article-title":"Uniprot: the universal protein knowledgebase in 2025","volume":"53","year":"2025","journal-title":"Nucleic Acids Res"},{"key":"B7","doi-asserted-by":"publisher","first-page":"e2430","DOI":"10.1002\/mgg3.2430","article-title":"Clinical and genetic characteristics of three patients with congenital insensitivity to pain with anhidrosis: case reports and a review of the literature","volume":"12","author":"Cho","year":"2024","journal-title":"Mol Genet Genomic Med"},{"key":"B8","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1038\/ng0896-485","article-title":"Mutations in the TRKA\/NGF receptor gene in patients with congenital insensitivity to pain with anhidrosis","volume":"13","author":"Indo","year":"1996","journal-title":"Nat Genet"},{"key":"B9","doi-asserted-by":"publisher","first-page":"344","DOI":"10.3390\/children12030344","article-title":"Recurrent osteomyelitis in a paediatric patient with a novel NTRK1 mutation: a case report on congenital insensitivity to pain with anhidrosis","volume":"12","author":"Gasina","year":"2025","journal-title":"Children (Basel)"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1926","DOI":"10.1097\/j.pain.0000000000003252","article-title":"Genetic etiology study in a large cohort with congenital insensitivity to pain with anhidrosis","volume":"165","author":"Li","year":"2024","journal-title":"Pain"},{"key":"B11","doi-asserted-by":"publisher","first-page":"1668","DOI":"10.1177\/0883073812462626","article-title":"Atypical hereditary sensory and autonomic neuropathy type IV with neither mental retardation nor pain insensitivity","volume":"28","author":"Jung","year":"2013","journal-title":"J Child Neurol"},{"key":"B12","doi-asserted-by":"publisher","first-page":"1904","DOI":"10.1111\/os.13746","article-title":"From the destruction of two lumbar segments to thoracic-lumbar-pelvic fusion: a case caused by congenital insensitivity to pain with anhidrosis and literature review","volume":"15","author":"Jiao","year":"2023","journal-title":"Orthop Surg"},{"key":"B13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.4103\/0019-5154.103080","article-title":"Congenital insensitivity to pain and anhidrosis: a case report from South India","volume":"57","author":"Udayashankar","year":"2012","journal-title":"Indian J Dermatol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"105636","DOI":"10.1016\/j.clineuro.2019.105636","article-title":"Congenital insensitivity to pain with anhidrosis syndrome: a series from Jordan","volume":"189","author":"Masri","year":"2020","journal-title":"Clin Neurol Neurosurg"},{"key":"B15","doi-asserted-by":"publisher","first-page":"26330040241292378","DOI":"10.1177\/26330040241292378","article-title":"Congenital insensitivity to pain with anhidrosis: a literature review and the advocacy for stem cell therapeutic interventions","volume":"5","author":"Ikrama","year":"2024","journal-title":"Ther Adv Rare Dis"},{"key":"B16","doi-asserted-by":"publisher","first-page":"4880","DOI":"10.1093\/brain\/awad328","article-title":"Genetic landscape of congenital insensitivity to pain and hereditary sensory and autonomic neuropathies","volume":"146","author":"Lischka","year":"2023","journal-title":"Brain"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1844909\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T05:47:09Z","timestamp":1779256029000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2026.1844909\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":16,"alternative-id":["10.3389\/fped.2026.1844909"],"URL":"https:\/\/doi.org\/10.3389\/fped.2026.1844909","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1844909"}}