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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...

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Autores principales: 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
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
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.
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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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