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Most disease\u2010causing variants identified to date are putative loss\u2010of\u2010function alleles, although 15\u201320% of cases are attributed to missense variants. We describe here four patients (including one previously published patient) with de novo <jats:italic>KMT2D<\/jats:italic> missense variants and with shared but unusual clinical findings not typically seen in Kabuki syndrome, including athelia (absent nipples), choanal atresia, hypoparathyroidism, delayed or absent pubertal development, and extreme short stature. These individuals also lack the typical dysmorphic facial features found in Kabuki syndrome. Two of the four patients had severe interstitial lung disease. All of these variants cluster within a 40\u2010amino\u2010acid region of the protein that is located just N\u2010terminal of an annotated coiled coil domain. These findings significantly expand the phenotypic spectrum of features associated with variants in <jats:italic>KMT2D<\/jats:italic> beyond those seen in Kabuki syndrome and suggest a possible new underlying disease mechanism for these patients.<\/jats:p>","DOI":"10.1002\/ajmg.a.61518","type":"journal-article","created":{"date-parts":[[2020,2,21]],"date-time":"2020-02-21T13:26:49Z","timestamp":1582291609000},"page":"1053-1065","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Phenotypic expansion of <i>KMT2D\u2010<\/i>related disorder: Beyond Kabuki syndrome"],"prefix":"10.1002","volume":"182","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6027-6020","authenticated-orcid":false,"given":"Dustin","family":"Baldridge","sequence":"first","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca C.","family":"Spillmann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Division of Medical Genetics Duke University Medical Center  Durham North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel J.","family":"Wegner","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer A.","family":"Wambach","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frances V.","family":"White","sequence":"additional","affiliation":[{"name":"Department of Pathology and Immunology Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen","family":"Sisco","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomi L.","family":"Toler","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patricia I.","family":"Dickson","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Washington University School of Medicine  St. Louis Missouri USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"F. 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