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These variants were historically believed to be incompatible with life in males; however, recent advances in genetic testing have revealed significant clinical heterogeneity. The current study aimed to improve our understanding of diagnostic experiences in males with confirmed pathogenic alteration of <jats:italic>MECP2<\/jats:italic>. An international sample of caregivers completed a survey of diagnostic experiences (<jats:italic>N<\/jats:italic>\u2009=\u200947) and phenomenological interviews (<jats:italic>n<\/jats:italic>\u2009=\u200932). Median [interquartile range; IQR] age of genetic diagnosis was 3\u2009years [1.08, 6.75]. Multivariate analysis showed that for every year increase in year of birth, age of diagnosis (in years) decreased by 0.31. Qualitative findings demonstrate that medical biases and widespread misconceptions contribute to delays in accurate clinical diagnosis, which negatively impacts child health and family functioning. As genetic testing becomes more widely available, age of genetic diagnosis is decreasing, resulting in more providers and families with unexpected results and a notable lack of male\u2010specific anticipatory guidance and clinical recommendations. Diagnostic providers must increase their awareness of males with confirmed pathogenic alterations of <jats:italic>MECP2<\/jats:italic> and be prepared to deliver the diagnosis with empathy and accurate, up\u2010to\u2010date information on prognosis and treatment options.<\/jats:p>","DOI":"10.1002\/ajmg.a.64147","type":"journal-article","created":{"date-parts":[[2025,6,14]],"date-time":"2025-06-14T08:21:09Z","timestamp":1749889269000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Medical Biases and Misconceptions Impact Diagnoses in Males With Loss of Function <scp><i>MECP2<\/i><\/scp> Variants"],"prefix":"10.1002","volume":"197","author":[{"given":"Talia","family":"Thompson","sequence":"first","affiliation":[{"name":"Pediatrics University of Colorado School of Medicine, Children's Hospital Colorado  Aurora Colorado USA"},{"name":"Accords University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dennis","family":"Gurfinkel","sequence":"additional","affiliation":[{"name":"Accords University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lori","family":"Silveira","sequence":"additional","affiliation":[{"name":"Pediatrics University of Colorado School of Medicine, Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9966-0160","authenticated-orcid":false,"given":"Natalia","family":"Klamut","sequence":"additional","affiliation":[{"name":"Pediatrics University of Colorado School of Medicine, Children's Hospital Colorado  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kate","family":"Ferdinandsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Fu","sequence":"additional","affiliation":[{"name":"Pediatrics Vanderbilt Kennedy Center, Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9671-2883","authenticated-orcid":false,"given":"Amitha L.","family":"Ananth","sequence":"additional","affiliation":[{"name":"Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane B.","family":"Lane","sequence":"additional","affiliation":[{"name":"Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"University of Pennsylvania Perelman School of Medicine, Children's Hospital of Philadelphia  Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Neul","sequence":"additional","affiliation":[{"name":"Pediatrics Vanderbilt Kennedy Center, Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan K.","family":"Percy","sequence":"additional","affiliation":[{"name":"Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Benke","sequence":"additional","affiliation":[{"name":"Pediatrics University of Colorado School of Medicine, Children's Hospital Colorado  Aurora Colorado USA"},{"name":"Pharmacology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Neurology University of Colorado School of Medicine  Aurora Colorado USA"},{"name":"Otolaryngology University of Colorado School of Medicine  Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,14]]},"reference":[{"key":"e_1_2_13_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_13_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pediatrneurol.2024.09.022"},{"key":"e_1_2_13_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36525"},{"key":"e_1_2_13_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023\u2010022\u201002358\u2010x"},{"key":"e_1_2_13_6_1","volume-title":"Introduction to Phenomenology: Focus on Methodology","author":"Beck C. 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