{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T01:04:54Z","timestamp":1760058294217,"version":"build-2065373602"},"reference-count":29,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T00:00:00Z","timestamp":1742428800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Congenital adrenal hyperplasia (CAH) represents a group of autosomal recessive disorders characterized by impaired cortisol synthesis in the adrenal glands. Over 90% of CAH cases result from a deficiency of the enzyme 21-hydroxylase (21OHD). The clinical spectrum of 21OHD ranges from the severe, life-threatening salt-wasting classic form, often presenting with prenatal virilization in females, to the non-classic (milder) form, which lacks glucocorticoid deficiency. Females with the non-classic form may experience symptoms of hyperandrogenism or infertility later in life, while males with non-classic CAH are often undiagnosed due to the subtler presentation. The coexistence of genetic anomalies and CAH is rarely reported in the literature, particularly in cases involving Triple X syndrome\u2014a condition typically associated with a mild and frequently underdiagnosed clinical course. Case presentation: Here, we present a unique case of a 38-year-old woman with a history of premature ovarian failure and subsequent clinical features of hyperandrogenism. Further investigation revealed a novel association between partial 21OHD and a Triple X karyotype\u2014an association not previously documented in the literature. Conclusions: This case highlights the potential for coexisting rare genetic conditions and underscores the critical importance of thorough and meticulous clinical evaluation.<\/jats:p>","DOI":"10.3390\/genes16030354","type":"journal-article","created":{"date-parts":[[2025,3,20]],"date-time":"2025-03-20T07:59:54Z","timestamp":1742457594000},"page":"354","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Unique Case Report: A Rare Association of 21-Hydroxylase Deficiency with Triple X Karyotype"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6097-8145","authenticated-orcid":false,"given":"Rossana Santiago","family":"de Sousa Azulay","sequence":"first","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1465-860X","authenticated-orcid":false,"given":"Alexandre Nogueira","family":"Facundo","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sarah Sousa e","family":"Sousa","sequence":"additional","affiliation":[{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gilvan Cortes","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0464-4343","authenticated-orcid":false,"given":"Marcelo","family":"Magalh\u00e3es","sequence":"additional","affiliation":[{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6726-4786","authenticated-orcid":false,"given":"Clariano Pires","family":"de Oliveira Neto","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5124-7394","authenticated-orcid":false,"given":"Joana D\u2019arc Matos Fran\u00e7a","family":"de Abreu","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9311-5047","authenticated-orcid":false,"given":"D\u00e9bora Cristina Ferreira","family":"Lago","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sabrina","family":"da Silva Pereira Damianse","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Viviane Chaves","family":"de Carvalho","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caio Andrade","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6785-7864","authenticated-orcid":false,"given":"Vandilson Pinheiro","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fernanda Borchers","family":"Coeli-Lacchini","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo 14048-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4932-4623","authenticated-orcid":false,"given":"Margaret","family":"de Castro","sequence":"additional","affiliation":[{"name":"Department of Medicine, Ribeirao Preto Medical School, University of Sao Paulo, Sao Paulo 14048-900, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"dos Santos Faria","sequence":"additional","affiliation":[{"name":"Service of Endocrinology, University Hospital of the Federal University of Maranh\u00e3o (HUUFMA\/EBSERH), S\u00e3o Luis 65020-070, Brazil"},{"name":"Research Group in Endocrinology and Clinical and Molecular Metabolism (ENDOCLIM), S\u00e3o Luis 65020-040, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"477","DOI":"10.1055\/a-1108-1419","article-title":"Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency: An Update on Genetic Analysis of CYP21A2 Gene","volume":"129","author":"Carvalho","year":"2021","journal-title":"Exp. 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Endocrinol., 12.","DOI":"10.3389\/fendo.2021.788812"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2194","DOI":"10.1016\/S0140-6736(17)31431-9","article-title":"Congenital adrenal hyperplasia","volume":"390","author":"Arlt","year":"2017","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"R127","DOI":"10.1530\/EJE-18-0712","article-title":"MANAGEMENT OF ENDOCRINE DISEASE: Diagnosis and management of the patient with non-classic CAH due to 21-hydroxylase deficiency","volume":"180","author":"Falhammar","year":"2019","journal-title":"Eur. J. Endocrinol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1248","DOI":"10.1056\/NEJMra1909786","article-title":"Congenital Adrenal Hyperplasia Due to 21-Hydroxylase Deficiency","volume":"383","author":"Merke","year":"2020","journal-title":"N. Engl. J. 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