{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,19]],"date-time":"2026-10-19T13:43:44Z","timestamp":1792417424092,"version":"4.4.0"},"reference-count":25,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T00:00:00Z","timestamp":1629158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>KBG syndrome is a neurodevelopmental autosomal dominant disorder characterized by short stature, macrodontia, developmental delay, behavioral problems, speech delay and delayed closing of fontanels. Most patients with KBG syndrome are found to have a mutation in the ANKRD11 gene or a chromosomal rearrangement involving this gene. We hereby present clinical evaluations of 23 patients aged 4 months to 26 years manifesting clinical features of KBG syndrome. Mutation analysis in the patients was performed using panel or exome sequencing and array CGH. Besides possessing dysmorphic features typical of the KBG syndrome, nearly all patients had psychomotor hyperactivity (86%), 81% had delayed speech, 61% had poor weight gain, 56% had delayed closure of fontanel and 56% had a hoarse voice. Macrodontia and a height range of \u22121 SDs to \u22122 SDs were noted in about half of the patients; only two patients presented with short stature below \u22123 SDs. The fact that wide, delayed closing fontanels were observed in more than half of our patients with KBG syndrome confirms the role of the ANKRD11 gene in skull formation and suture fusion. This clinical feature could be key to the diagnosis of KBG syndrome, especially in young children. Hoarse voice is a previously undescribed phenotype of KBG syndrome and could further reinforce clinical diagnosis.<\/jats:p>","DOI":"10.3390\/genes12081257","type":"journal-article","created":{"date-parts":[[2021,8,17]],"date-time":"2021-08-17T21:27:40Z","timestamp":1629235660000},"page":"1257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Wide Fontanels, Delayed Speech Development and Hoarse Voice as Useful Signs in the Diagnosis of KBG Syndrome: A Clinical Description of 23 Cases with Pathogenic Variants Involving the ANKRD11 Gene or Submicroscopic Chromosomal Rearrangements of 16q24.3"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5295-7363","authenticated-orcid":false,"given":"Anna","family":"Kutkowska-Ka\u017amierczak","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Boczar","sequence":"additional","affiliation":[{"name":"Pediatric Surgery Clinic, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kalka","sequence":"additional","affiliation":[{"name":"Unit of Anthropology, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Casta\u00f1eda","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakub","family":"Klapecki","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Pietrzyk","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics and Pathomorphology, University of Zielona G\u00f3ra, 65-417 Zielona G\u00f3ra, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Artur","family":"Barczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olga","family":"Malinowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aleksandra","family":"Landowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomasz","family":"Gambin","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9867-063X","authenticated-orcid":false,"given":"Katarzyna","family":"Kowalczyk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Wi\u015bniowiecka-Kowalnik","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Smyk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5102-8722","authenticated-orcid":false,"given":"Mateusz","family":"Dawidziuk","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8205-375X","authenticated-orcid":false,"given":"Katarzyna","family":"Niepok\u00f3j","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magdalena","family":"Paczkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pawe\u0142","family":"Szyld","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Lipska-Zi\u0119tkiewicz","sequence":"additional","affiliation":[{"name":"Rare Diseases Centre, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"},{"name":"Clinical Genetics Unit, Department of Biology and Medical Genetics, Faculty of Medicine, Medical University of Gda\u0144sk, 80-210 Gda\u0144sk, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8803-646X","authenticated-orcid":false,"given":"Krzysztof","family":"Szcza\u0142uba","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Kostyk","sequence":"additional","affiliation":[{"name":"Genetic Counselling Unit Kostyk&Kruczek, 31-436 Krak\u00f3w, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agata","family":"Runge","sequence":"additional","affiliation":[{"name":"Genetic Department, Ludwik Rydygier Collegium Medicum in Bydgoszcz, Nicolaus Copernicus University of Toru\u0144, 85-067 Bydgoszcz, Poland"},{"name":"Genetic Counselling Clinic, Antoni Jurasz University Hospital, 05-094 Bydgoszcz, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6688-2593","authenticated-orcid":false,"given":"Karolina","family":"Rutkowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6286-5526","authenticated-orcid":false,"given":"Rafa\u0142","family":"P\u0142oski","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Warsaw Medical University, 02-106 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beata","family":"Nowakowska","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerzy","family":"Bal","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ewa","family":"Obersztyn","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monika","family":"Gos","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Institute of the Mother and Child, Kasprzaka 17a, 01-211 Warsaw, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1002\/ajmg.a.30292","article-title":"KBG syndrome in a cohort of Italian patients","volume":"131A","author":"Brancati","year":"2004","journal-title":"Am. 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