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Here, we present three additional cases of this syndrome. Proband 1 was a 7\u2010year\u2010old female who presented with developmental delay, right\u2010leg hemihypertrophy, laryngeal cleft, esotropia, abnormal skin pigmentation, sectoral iris hypopigmentation, dysphagia, periventricular nodular heterotopia, seizures, morbid obesity, and a pelvic kidney. Genome sequencing (GS) revealed a\n                    <jats:italic>MED12L<\/jats:italic>\n                    variant, NM_053002.5:c.3559+2T&gt;G. Both computational models and transcriptomic analysis confirmed that this variant induced splice loss of\n                    <jats:italic>MED12L<\/jats:italic>\n                    exon 25. Probands 2 and 3 presented with overlapping phenotypes of developmental delay; sequencing confirmed c.3441_3444dup; p.(G1149Nfs*13) and seq[GRCh37] del(3)(q25.1q25.1) chr3:g.?_151075120 variants affecting\n                    <jats:italic>MED12L<\/jats:italic>\n                    . Further investigation found diploid\u2013triploid mosaicism in Proband 1, supporting the hypothesis that loss of\n                    <jats:italic>MED12L<\/jats:italic>\n                    function may increase risk for other cytogenetic abnormalities. Probands 2 and 3 did not harbor evidence of additional cytogenetic aberrations. In Proband 1, caloric restriction and semaglutide\u2013pramlintide combination therapy were started at age eight and were effective in weight reduction. Overall, this report expands the phenotypic spectrum of Nizon\u2010Isidor syndrome, highlights a potential link between\n                    <jats:italic>MED12L<\/jats:italic>\n                    and cytogenetic abnormalities, and demonstrates a case of weight loss through GLP\u20101 therapy in a child with a genetic obesity syndrome.\n                  <\/jats:p>","DOI":"10.1002\/ajmg.a.64233","type":"journal-article","created":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T09:43:18Z","timestamp":1755769398000},"page":"205-214","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Case Series of Nizon\u2010Isidor Syndrome by Heterozygous Variants in\n                    <i>MED12L<\/i>\n                    With Further Evidence of Mitotic Instability in One Case With Diploid\u2013Triploid Mosaicism"],"prefix":"10.1002","volume":"200","author":[{"given":"Russell","family":"Stewart","sequence":"first","affiliation":[{"name":"Vanderbilt University School of Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7200-7644","authenticated-orcid":false,"given":"Kimberly M.","family":"Ezell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics and Genomic Medicine Vanderbilt University Medical Center  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0569-6858","authenticated-orcid":false,"given":"Deanna S.","family":"Bell","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Program for Children With Medical Complexity Vanderbilt University Medical Center  Nashville Tennessee 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