{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T16:46:15Z","timestamp":1791477975922,"version":"4.3.4"},"reference-count":10,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T00:00:00Z","timestamp":1524614400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2018,6]]},"abstract":"<jats:p><jats:italic>KIAA2022<\/jats:italic> is an X\u2010linked intellectual disability (XLID) syndrome affecting males more severely than females. Few males with <jats:italic>KIAA2022<\/jats:italic> variants and XLID have been reported. We present a clinical report of two unrelated males, with two nonsense <jats:italic>KIAA2022<\/jats:italic> pathogenic variants, with profound intellectual disabilities, limited language development, strikingly similar autistic behavior, delay in motor milestones, and postnatal growth restriction. Patient 1, 19\u2010years\u2010old, has long ears, deeply set eyes with keratoconus, strabismus, a narrow forehead, anteverted nares, caf\u00e9\u2010au\u2010lait spots, macroglossia, thick vermilion of the upper and lower lips, and prognathism. He has gastroesophageal reflux, constipation with delayed rectosigmoid colonic transit time, difficulty regulating temperature, several musculoskeletal issues, and a history of one grand mal seizure. Patient 2, 10\u2010years\u2010old, has mild dysmorphic features, therapy resistant vomiting with diminished motility of the stomach, mild constipation, cortical visual impairment with intermittent strabismus, axial hypotonia, difficulty regulating temperature, and cutaneous mastocytosis. Genetic testing identified <jats:italic>KIAA2022<\/jats:italic> variant c.652C\u2009&gt;\u2009T(p.Arg218*) in Patient 1, and a novel nonsense <jats:italic>de novo<\/jats:italic> variant c.2707G\u2009&gt;\u2009T(p.Glu903*) in Patient 2. We also summarized features of all reported males with <jats:italic>KIAA2022<\/jats:italic> variants to date. This report not only adds knowledge of a novel pathogenic variant to the <jats:italic>KIAA2022<\/jats:italic> variant database, but also likely extends the spectrum by describing novel dysmorphic features and medical conditions including macroglossia, caf\u00e9\u2010au\u2010lait spots, keratoconus, severe cutaneous mastocytosis, and motility problems of the GI tract, which may help physicians involved in the care of patients with this syndrome. Lastly, we describe the power of social media in bringing families with rare medical conditions together.<\/jats:p>","DOI":"10.1002\/ajmg.a.38667","type":"journal-article","created":{"date-parts":[[2018,4,25]],"date-time":"2018-04-25T15:47:06Z","timestamp":1524671226000},"page":"1455-1462","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Clinical spectrum of <i>KIAA2022<\/i> pathogenic variants in males: Case report of two boys with <i>KIAA2022<\/i> pathogenic variants and review of the literature"],"prefix":"10.1002","volume":"176","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8203-2799","authenticated-orcid":false,"given":"Melissa","family":"Lorenzo","sequence":"first","affiliation":[{"name":"Faculty of Medicine Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Stolte\u2010Dijkstra","sequence":"additional","affiliation":[{"name":"Department of Genetics University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"van Rheenen","sequence":"additional","affiliation":[{"name":"Department of Pediatric Gastroenterology University Medical Center Groningen, University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald Garth","family":"Smith","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tom","family":"Scheers","sequence":"additional","affiliation":[{"name":"Department of Child and Adolescent Psychiatry University of Groningen Groningen The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jagdeep S.","family":"Walia","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Queen's University Kingston Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,4,25]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36274"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.2004.021626"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12528"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2016-103909"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37479"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37002"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.02.018"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.b.32355"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddt187"},{"key":"e_1_2_9_11_1","first-page":"1","article-title":"De novo loss of function mutations in KIAA2022 are associated with epilepsy and neurodevelopmental delay in females","volume":"2022","author":"Webster R.","year":"2016","journal-title":"Clinical Genetics"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.38667","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.38667","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T15:51:23Z","timestamp":1695484283000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.38667"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,4,25]]},"references-count":10,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2018,6]]}},"alternative-id":["10.1002\/ajmg.a.38667"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.38667","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,4,25]]},"assertion":[{"value":"2017-05-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-02-16","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2018-04-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}