{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T00:03:25Z","timestamp":1768435405305,"version":"3.49.0"},"reference-count":45,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,7,19]],"date-time":"2025-07-19T00:00:00Z","timestamp":1752883200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Italian Ministry of Health"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Children"],"abstract":"<jats:p>Background: Differences of sex development (DSD) are a group of congenital conditions characterized by atypical development of genital structures. The diagnosis is complex and involves clinical, hormonal, and genetic evaluations. Objective: To describe the clinical profile, diagnosis, and management of patients with DSD, with particular attention to genetic diagnosis. Study design: Retrospective study from a tertiary care pediatric hospital in Italy. Methods: 420 patients with DSD referred to the Endocrine Unit of Bambino Ges\u00f9 Children\u2019s Hospital in Rome, Italy, between 2016 and 2023 were included. Results: 75 patients had a 46,XY karyotype, 135 had a 46,XX karyotype, and 210 had chromosomal mosaicism. In our group of pediatric DSD patients, 21\/420 patients were born from pregnancies induced with assisted reproduction techniques (ICSI\/FIVET). Of these 21 patients, 5 had sex chromosome mosaicism. Using next-generation sequencing (NGS), we identified three new genetic variants: one in the AR gene, one in the NR5A1 gene, and one in the SRY gene. The use of NGS significantly improved the diagnostic yield, and a definitive diagnosis was reached in 84.76% of the entire cohort. Conclusions: This study highlights the challenges in the management of patients with DSD from early recognition to treatment and follow-up. A multidisciplinary approach is essential for a comprehensive evaluation of these conditions and to understand the role and clinical significance of the genetic variants.<\/jats:p>","DOI":"10.3390\/children12070954","type":"journal-article","created":{"date-parts":[[2025,7,21]],"date-time":"2025-07-21T11:44:05Z","timestamp":1753098245000},"page":"954","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Differences of Sex Development: A Study of 420 Patients from a Single Tertiary Pediatric Endocrinology Center"],"prefix":"10.3390","volume":"12","author":[{"given":"Silvia","family":"Ventresca","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University Hospital Arcispedale Sant\u2019Anna, University of Ferrara, 44124 Ferrara, Italy"},{"name":"Pediatrics Unit, Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0388-4337","authenticated-orcid":false,"given":"Laura","family":"Chioma","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Endocrinology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0582-2017","authenticated-orcid":false,"given":"Rosario","family":"Ruta","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2228-8271","authenticated-orcid":false,"given":"Mafalda","family":"Mucciolo","sequence":"additional","affiliation":[{"name":"Translational Cytogenomics Research Unit, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pasquale","family":"Parisi","sequence":"additional","affiliation":[{"name":"Pediatrics Unit, Department of Neuroscience, Mental Health and Sense Organs (NESMOS), Faculty of Medicine and Psychology, Sapienza University of Rome, 00185 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnese","family":"Suppiej","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University Hospital Arcispedale Sant\u2019Anna, University of Ferrara, 44124 Ferrara, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sandro","family":"Loche","sequence":"additional","affiliation":[{"name":"Research Unit for Innovative Therapies in Endocrinopathies, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5647-7519","authenticated-orcid":false,"given":"Marco","family":"Cappa","sequence":"additional","affiliation":[{"name":"Research Unit for Innovative Therapies in Endocrinopathies, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5616-9185","authenticated-orcid":false,"given":"Carla","family":"Bizzarri","sequence":"additional","affiliation":[{"name":"Unit of Pediatric Endocrinology, Bambino Ges\u00f9 Children\u2019s Hospital, IRCCS, Piazza S. Onofrio 4, 00165 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,7,19]]},"reference":[{"key":"ref_1","unstructured":"Feingold, K.R., Ahmed, S.F., Anawalt, B., Blackman, M.R., Boyce, A., Chrousos, G., Corpas, E., de Herder, W.W., Dhatariya, K., and Dungan, K. (2023). Ambiguous Genitalia in the Newborn. Endotext, MDText.com, Inc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1080\/00224490209552139","article-title":"How common is intersex? A response to Anne Fausto-Sterling","volume":"39","author":"Sax","year":"2002","journal-title":"J. Sex Res."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e488","DOI":"10.1542\/peds.2006-0738","article-title":"International Consensus Conference on Intersex organized by the Lawson Wilkins Pediatric Endocrine Society and the European Society for Paediatric Endocrinology. Consensus statement on management of intersex disorders. 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