{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T02:05:39Z","timestamp":1772503539074,"version":"3.50.1"},"reference-count":23,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T00:00:00Z","timestamp":1698969600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molec Gen &amp;amp; Gen Med"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Kabuki syndrome 1 (KS1; OMIM:147920), which is characterized by distinctive dysmorphic facial features (such as arched eyebrows, long palpebral fissures with eversion of the lower lid, and large protuberant ears), intellectual disability, short stature, and dermatoglyphic and skeletal abnormalities, is brought on by pathogenic variants in <jats:italic>KMT2D<\/jats:italic> (OMIM:602113). In this work, three individuals with novel pathogenic <jats:italic>KMT2D<\/jats:italic> gene variants had their longitudinal audiological manifestations and ear structural characteristics outlined.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The longitudinal audiological data from neonatal hearing screening and a battery of several hearing tests were evaluated. The battery of hearing tests included tympanometry, distortion product otoacoustic emission (DPOAE), click\u2010evoked air\u2010conduction auditory brain\u2010stem response (AC\u2010ABR), click\u2010evoked bone\u2010conduction auditory brain\u2010stem response (BC\u2010ABR), narrow band CE\u2010chirp auditory steady\u2010state response (NB CE\u2010chirp ASSR), and pure\u2010tone audiometry (PTA). Phenotype identification and whole exome sequencing (WES) were performed on recruited individuals.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>All three patients (two females and on male; last evaluations at 14\u2009months, 11\u2009months, and 5.7\u2009years, respectively) failed the newborn hearing screening, and the audiological follow\u2010up data revealed mild to profound fluctuating hearing loss, which was directly influenced by the incidence and severity of otitis media with effusion (OME). When OME occurred, the AC\u2010ABR thresholds increased from 30\u201375 dBnHL to 45\u201390 dBnHL. The threshold for the BC\u2010ABR and BC\u2010PTA was between 25 and 50 dBnHL, indicating mild to moderate sensorineural hearing loss (SNHL). The high\u2010resolution computed tomography (HRCT) pictures indicated that all three patients had middle and inner ear abnormalities. Middle ear anomalies showed as diminished mastoid gasification and ossicle dysplasia. Cochlear dysplasia, a dilated vestibule, fusion of the vestibule with the horizontal semicircular canals, and a short and thick horizontal semicircular canal were visible on images of the inner ear. This study recruited three individuals with three novel pathogenic variants (c.5104C&gt;T, c.10205delA, and c.12840delC) of <jats:italic>KMT2D<\/jats:italic> who were identified at ages 27\u2009days, 2\u2009months, and 5.5\u2009years.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Hearing characteristics of three individuals with three novel pathogenic variants of <jats:italic>KMT2D<\/jats:italic> range from mild to profound fluctuating hearing loss with mild to moderate SNHL. HRCT scans showed that all three individuals had anatomical middle and inner ear abnormalities. KS 1 patients must get clinical therapy for OME, frequent auditory monitoring, and prompt intervention.<\/jats:p><\/jats:sec>","DOI":"10.1002\/mgg3.2306","type":"journal-article","created":{"date-parts":[[2023,11,3]],"date-time":"2023-11-03T11:20:12Z","timestamp":1699010412000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hearing characteristics and otoradiological abnormalities in three patients with novel pathogenic variants of <scp><i>KMT2D<\/i>\u2010related<\/scp> Kabuki syndrome"],"prefix":"10.1002","volume":"12","author":[{"given":"Zhoushu","family":"Zheng","sequence":"first","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Meihong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yinghui","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yihui","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ming","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Yinzhou No.2 Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liangjiong","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Radiology Ningbo Medical Center Lihuili Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junhua","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9309-6632","authenticated-orcid":false,"given":"Haibo","family":"Li","sequence":"additional","affiliation":[{"name":"The Central Laboratory of Birth Defects Prevention and Control Ningbo Women and Children's Hospital  Ningbo China"},{"name":"Ningbo Key Laboratory for the Prevention and Treatment of Embryogenic Diseases Ningbo Women and Children's Hospital  Ningbo China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,11,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2018-105625"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.61518"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/14992020600690951"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.32610"},{"key":"e_1_2_11_6_1","unstructured":"Busa J. 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(2007).\u201cYear 2007 Position Statement: Principles and Guidelines for Early Hearing Detection and Intervention Programs.\u201d Pediatrics.American Academy of Pediatrics.https:\/\/doi.org\/10.1542\/peds.2007\u20102333"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF02026678"},{"key":"e_1_2_11_8_1","volume-title":"Kabuki syndrome","author":"Chen H.","year":"2006"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1121\/1.428438"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2013.05.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejrad.2007.10.019"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80256-9"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12881-015-0171-4"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/cge.12081"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.646"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-3476(81)80255-7"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.13201\/j.issn.1001\u20101781.2019.09.00"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2013.11.012"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-010-1831-3"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13023-019-1219-x"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1097\/AUD.0000000000000580"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijporl.2005.09.025"},{"key":"e_1_2_11_23_1","first-page":"99","article-title":"Deafness and Mondini dysplasia in Kabuki (Niikawa\u2010Kuroki) syndrome. 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