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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
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 rea...
Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394041/ https://www.ncbi.nlm.nih.gov/pubmed/34440431 http://dx.doi.org/10.3390/genes12081257 |
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author | Kutkowska-Kaźmierczak, Anna Boczar, Maria Kalka, Ewa Castañeda, Jennifer Klapecki, Jakub Pietrzyk, Aleksandra Barczyk, Artur Malinowska, Olga Landowska, Aleksandra Gambin, Tomasz Kowalczyk, Katarzyna Wiśniowiecka-Kowalnik, Barbara Smyk, Marta Dawidziuk, Mateusz Niepokój, Katarzyna Paczkowska, Magdalena Szyld, Paweł Lipska-Ziętkiewicz, Beata Szczałuba, Krzysztof Kostyk, Ewa Runge, Agata Rutkowska, Karolina Płoski, Rafał Nowakowska, Beata Bal, Jerzy Obersztyn, Ewa Gos, Monika |
author_facet | Kutkowska-Kaźmierczak, Anna Boczar, Maria Kalka, Ewa Castañeda, Jennifer Klapecki, Jakub Pietrzyk, Aleksandra Barczyk, Artur Malinowska, Olga Landowska, Aleksandra Gambin, Tomasz Kowalczyk, Katarzyna Wiśniowiecka-Kowalnik, Barbara Smyk, Marta Dawidziuk, Mateusz Niepokój, Katarzyna Paczkowska, Magdalena Szyld, Paweł Lipska-Ziętkiewicz, Beata Szczałuba, Krzysztof Kostyk, Ewa Runge, Agata Rutkowska, Karolina Płoski, Rafał Nowakowska, Beata Bal, Jerzy Obersztyn, Ewa Gos, Monika |
author_sort | Kutkowska-Kaźmierczak, Anna |
collection | PubMed |
description | 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 −1 SDs to −2 SDs were noted in about half of the patients; only two patients presented with short stature below −3 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. |
format | Online Article Text |
id | pubmed-8394041 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-83940412021-08-28 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 Kutkowska-Kaźmierczak, Anna Boczar, Maria Kalka, Ewa Castañeda, Jennifer Klapecki, Jakub Pietrzyk, Aleksandra Barczyk, Artur Malinowska, Olga Landowska, Aleksandra Gambin, Tomasz Kowalczyk, Katarzyna Wiśniowiecka-Kowalnik, Barbara Smyk, Marta Dawidziuk, Mateusz Niepokój, Katarzyna Paczkowska, Magdalena Szyld, Paweł Lipska-Ziętkiewicz, Beata Szczałuba, Krzysztof Kostyk, Ewa Runge, Agata Rutkowska, Karolina Płoski, Rafał Nowakowska, Beata Bal, Jerzy Obersztyn, Ewa Gos, Monika Genes (Basel) Article 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 −1 SDs to −2 SDs were noted in about half of the patients; only two patients presented with short stature below −3 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. MDPI 2021-08-17 /pmc/articles/PMC8394041/ /pubmed/34440431 http://dx.doi.org/10.3390/genes12081257 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Kutkowska-Kaźmierczak, Anna Boczar, Maria Kalka, Ewa Castañeda, Jennifer Klapecki, Jakub Pietrzyk, Aleksandra Barczyk, Artur Malinowska, Olga Landowska, Aleksandra Gambin, Tomasz Kowalczyk, Katarzyna Wiśniowiecka-Kowalnik, Barbara Smyk, Marta Dawidziuk, Mateusz Niepokój, Katarzyna Paczkowska, Magdalena Szyld, Paweł Lipska-Ziętkiewicz, Beata Szczałuba, Krzysztof Kostyk, Ewa Runge, Agata Rutkowska, Karolina Płoski, Rafał Nowakowska, Beata Bal, Jerzy Obersztyn, Ewa Gos, Monika 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 |
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 |
title_full | 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 |
title_fullStr | 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 |
title_full_unstemmed | 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 |
title_short | 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 |
title_sort | 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 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8394041/ https://www.ncbi.nlm.nih.gov/pubmed/34440431 http://dx.doi.org/10.3390/genes12081257 |
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