{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T17:18:08Z","timestamp":1787764688664,"version":"build-2784847793"},"reference-count":35,"publisher":"The Endocrine Society","license":[{"start":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T00:00:00Z","timestamp":1787702400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Eugenia Mart\u00ednez Vallejo (1674-1699), famously portrayed by Juan Carre\u00f1o de Miranda at the court of King Carlos II of Spain, has long been considered a historical example of Prader\u2013Willi syndrome (PWS). More than 20 publications have supported this diagnosis based on her severe obesity, facial appearance, and presumed small extremities. We revisited this diagnosis using historical medical documentation, auxological analysis, and next-generation phenotyping.<\/jats:p>\n                  <jats:p>Historical documents preserved from that period describe hyperphagia beginning immediately after birth, with a weight of 25\u2005kg at 1 year of age, inconsistent with the natural history of PWS, typically characterized in infancy by hypotonia and feeding difficulties. In addition, Eugenia\u2019s estimated height at age 6 years, derived from the dimensions of a life-size portrait, corresponds approximately to the 95th percentile for age, arguing against the short stature characteristic of PWS.<\/jats:p>\n                  <jats:p>Given these inconsistencies, we considered alternative diagnoses within the leptin\u2013melanocortin pathway disorders associated with severe early-onset obesity. Application of DeepGestalt facial phenotyping did not support PWS. Bardet\u2013Biedl syndrome (BBS) was suggested with low-to-moderate confidence. However, the absence of historical evidence for key syndromic features, including polydactyly, neurodevelopmental impairment, and progressive vision loss, makes BBS unlikely. Eugenia\u2019s accelerated linear growth and absence of overt syndromic or dysmorphic features are compatible with melanocortin receptor 4 deficiency, in which affected individuals typically present with isolated severe early-onset obesity.<\/jats:p>\n                  <jats:p>This case illustrates how integrating historical records, clinical reasoning, and AI-based phenotyping can challenge longstanding diagnostic assumptions and broaden the differential diagnosis of severe early-onset obesity.<\/jats:p>","DOI":"10.1210\/clinem\/dgag287","type":"journal-article","created":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T11:42:57Z","timestamp":1787658177000},"source":"Crossref","is-referenced-by-count":0,"title":["Diagnosing the canvas: challenging the diagnosis of Prader\u2013Willi syndrome in\n                    <i>Eugenia Mart\u00ednez<\/i>\n                    Vallejo (1674-1699)"],"prefix":"10.1210","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8983-464X","authenticated-orcid":false,"given":"Uri","family":"Hamiel","sequence":"first","affiliation":[{"name":"Genetics and Genomics Institute, Sourasky Medical Center , Tel Aviv 6423906 ,","place":["Israel"]},{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8365-8091","authenticated-orcid":false,"given":"Orit","family":"Pinhas-Hamiel","sequence":"additional","affiliation":[{"name":"Gray Faculty of Medical and Health Sciences, Tel Aviv University , Tel Aviv 6997801 ,","place":["Israel"]},{"name":"Pediatric Endocrine and Diabetes Division, Edmond and Lily Safra Children\u2019s Hospital, Sheba Medical Center , Ramat-Gan 5265601 ,","place":["Israel"]},{"name":"Juvenile Diabetes Center, Maccabi Health Care Services , Ra'anana 4330013 ,","place":["Israel"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","published-online":{"date-parts":[[2026,8,26]]},"reference":[{"issue":"10","key":"2026082612223761800_dgag287-B1","doi-asserted-by":"crossref","first-page":"1725","DOI":"10.1093\/rheumatology\/ket459","article-title":"Art and rheumatology: the artist and the rheumatologist\u2019s perspective","volume":"53","author":"Hinojosa-Azaola","year":"2014","journal-title":"Rheumatology"},{"issue":"5","key":"2026082612223761800_dgag287-B2","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ca.23363","article-title":"A hidden rib found in Michelangelo Buonarroti's fresco The Creation of Adam","volume":"32","author":"de Campos","year":"2019","journal-title":"Clin Anat"},{"key":"2026082612223761800_dgag287-B3","volume-title":"Relaci\u00f3n verdadera en que se da noticia de los prodigios de la naturaleza que han llegado a esta corte, en una ni\u00f1a gigante llamada Eugenia Mart\u00ednez de la 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