{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,8]],"date-time":"2026-05-08T01:35:05Z","timestamp":1778204105712,"version":"3.51.4"},"reference-count":11,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T00:00:00Z","timestamp":1744761600000},"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:sec><jats:title>Background<\/jats:title><jats:p>Rabson-Mendenhall Syndrome (RMS), a rare hereditary form of insulin resistance, is marked by severe hyperinsulinemia and early-onset acanthosis nigricans (AN) during childhood.<\/jats:p><\/jats:sec><jats:sec><jats:title>Case presentation<\/jats:title><jats:p>A case of a 15-month-old girl was reported, presenting with widespread acanthosis nigricans, growth retardation, dysmorphic facial features, and hypertrichosis. Laboratory results indicated fasting hypoglycemia and hyperinsulinemia, while her oral glucose tolerance test (OGTT) remained normal. Whole-exome sequencing revealed two novel mutations in the insulin receptor gene (INSR): a c.3392 C\u2009&amp;gt;\u2009G missense\/frameshift mutation in exon 19 and a c.4007_4010delAGAG deletion in exon 22.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Acanthosis nigricans (AN) can serve as a clinical marker that strongly suggests underlying metabolic syndromes, making genetic analysis essential for confirming the diagnosis.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fped.2025.1511429","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T05:27:26Z","timestamp":1744781246000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Rabson-Mendenhall syndrome presented as severe acanthosis nigricans in an infant harboring novel mutations in the INSR gene: a case report"],"prefix":"10.3389","volume":"13","author":[{"given":"Shi","family":"Yan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Sheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hai-zhen","family":"Hui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun-yan","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"De-ming","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,16]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1016\/j.clindermatol.2017.09.008","article-title":"Acanthosis nigricans and the metabolic syndrome","volume":"36","author":"Kaeada\u011f","year":"2018","journal-title":"Clin Dermatol"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1465","DOI":"10.1093\/hmg\/11.12.1465","article-title":"Genotype-phenotype correlation in inherited severe insulin resistance","volume":"11","author":"Longo","year":"2002","journal-title":"Hum Mol Genet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1111\/pedi.12772","article-title":"ISPAD Clinical practice consensus guidelines 2018: the diagnosis and management of monogenic diabetes in children and adolescents","author":"Hattersley","year":"2018","journal-title":"Pediatr Diabetes"},{"key":"B4","doi-asserted-by":"publisher","first-page":"145","DOI":"10.1016\/j.beem.2011.09.003","article-title":"Metabolic insights from extreme human insulin resistance phenotypes","volume":"26","author":"Stears","year":"2012","journal-title":"Best Pract Res Clin Endocrinol Metab"},{"key":"B5","doi-asserted-by":"publisher","first-page":"114","DOI":"10.1073\/pnas.86.1.114","article-title":"Structure of the human insulin receptor gene and characterization of its promoter","volume":"86","author":"Seino","year":"1989","journal-title":"Proc Nati Acad Sci U S A"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1186\/s13633-016-0039-1","article-title":"Rabson Mendenhall syndrome caused by a novel missense mutation","volume":"21","author":"Sinnarajah","year":"2016","journal-title":"Int J Pediatr Endocrinol"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2713","DOI":"10.2337\/db17-0301","article-title":"Structural basis and genotype-phenotype correlations of INSR mutations causing severe insulin resistance","volume":"66","author":"Hosoe","year":"2017","journal-title":"Diabetes"},{"key":"B8","doi-asserted-by":"publisher","first-page":"bvae123","DOI":"10.1210\/jendso\/bvae123","article-title":"Rabson-Mendenhall: analysis of the clinical characteristics and gene mutations in forty-two patients","volume":"8","author":"Gong","year":"2024","journal-title":"J Endocr Soc"},{"key":"B9","doi-asserted-by":"publisher","first-page":"606964","DOI":"10.3389\/fendo.2021.606964","article-title":"Clinical and functional characterization of novel INSR variants in two families with severe insulin resistance syndrome","volume":"12","author":"Zhou","year":"2021","journal-title":"Front Endocrinol (Lausanne)"},{"key":"B10","article-title":"INSR-related severe insulin resistance syndrome","author":"Mesika","year":"","journal-title":"GeneReviews\u00ae"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e1032","DOI":"10.1210\/clinem\/dgab782","article-title":"Long-term effects of metreleptin in rabson-mendenhall syndrome on glycemia, growth, and kidney function","volume":"107","author":"Okawa","year":"2022","journal-title":"J Clin Endocrinol Metab"}],"container-title":["Frontiers in Pediatrics"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1511429\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T05:27:27Z","timestamp":1744781247000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fped.2025.1511429\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,16]]},"references-count":11,"alternative-id":["10.3389\/fped.2025.1511429"],"URL":"https:\/\/doi.org\/10.3389\/fped.2025.1511429","relation":{},"ISSN":["2296-2360"],"issn-type":[{"value":"2296-2360","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,16]]},"article-number":"1511429"}}