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Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis

Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4. The objectives of this study were to report the most representative oral findings of WHS, relate them with other clinical characteristics of the disease, and establi...

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Autores principales: Limeres, Jacobo, Serrano, Candela, De Nova, Joaquin Manuel, Silvestre-Rangil, Javier, Machuca, Guillermo, Maura, Isabel, Cruz Ruiz-Villandiego, Jose, Diz, Pedro, Blanco-Lago, Raquel, Nevado, Julian, Diniz-Freitas, Marcio
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694380/
https://www.ncbi.nlm.nih.gov/pubmed/33158290
http://dx.doi.org/10.3390/jcm9113556
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author Limeres, Jacobo
Serrano, Candela
De Nova, Joaquin Manuel
Silvestre-Rangil, Javier
Machuca, Guillermo
Maura, Isabel
Cruz Ruiz-Villandiego, Jose
Diz, Pedro
Blanco-Lago, Raquel
Nevado, Julian
Diniz-Freitas, Marcio
author_facet Limeres, Jacobo
Serrano, Candela
De Nova, Joaquin Manuel
Silvestre-Rangil, Javier
Machuca, Guillermo
Maura, Isabel
Cruz Ruiz-Villandiego, Jose
Diz, Pedro
Blanco-Lago, Raquel
Nevado, Julian
Diniz-Freitas, Marcio
author_sort Limeres, Jacobo
collection PubMed
description Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4. The objectives of this study were to report the most representative oral findings of WHS, relate them with other clinical characteristics of the disease, and establish possible phenotype-genotype correlation. Methods: The study was conducted at 6 reference centers distributed throughout Spain during 2018–2019. The study group consisted of 31 patients with WHS who underwent a standardized oral examination. Due to behavioral reasons, imaging studies were performed on only 11 of the children 6 years of age or older. All participants had previously undergone a specific medical examination for WHS, during which anatomical, functional, epilepsy-related, and genetic variables were recorded. Results: The most prevalent oral manifestations were delayed tooth eruption (74.1%), bruxism (64.5%), dental agenesis (63.6%), micrognathia (60.0%), oligodontia (45.5%), and downturned corners of the mouth (32.3%). We detected strong correlation between psychomotor delay and oligodontia (p = 0.008; Cramér’s V coefficient, 0.75). The size of the deletion was correlated in a statistically significant manner with the presence of oligodontia (p = 0.009; point-biserial correlation coefficient, 0.75). Conclusion: Certain oral manifestations prevalent in WHS can form part of the syndrome’s phenotypic variability. A number of the characteristics of WHS, such as psychomotor delay and epilepsy, are correlated with oral findings such as oligodontia and bruxism. Although most genotype-phenotype correlations are currently unknown, most of them seem to be associated with larger deletions, suggesting that some oral-facial candidate genes might be outside the critical WHS region, indicating that WHS is a contiguous gene syndrome.
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spelling pubmed-76943802020-11-28 Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis Limeres, Jacobo Serrano, Candela De Nova, Joaquin Manuel Silvestre-Rangil, Javier Machuca, Guillermo Maura, Isabel Cruz Ruiz-Villandiego, Jose Diz, Pedro Blanco-Lago, Raquel Nevado, Julian Diniz-Freitas, Marcio J Clin Med Article Background: Wolf-Hirschhorn syndrome (WHS) is a rare disease caused by deletion in the distal moiety of the short arm of chromosome 4. The objectives of this study were to report the most representative oral findings of WHS, relate them with other clinical characteristics of the disease, and establish possible phenotype-genotype correlation. Methods: The study was conducted at 6 reference centers distributed throughout Spain during 2018–2019. The study group consisted of 31 patients with WHS who underwent a standardized oral examination. Due to behavioral reasons, imaging studies were performed on only 11 of the children 6 years of age or older. All participants had previously undergone a specific medical examination for WHS, during which anatomical, functional, epilepsy-related, and genetic variables were recorded. Results: The most prevalent oral manifestations were delayed tooth eruption (74.1%), bruxism (64.5%), dental agenesis (63.6%), micrognathia (60.0%), oligodontia (45.5%), and downturned corners of the mouth (32.3%). We detected strong correlation between psychomotor delay and oligodontia (p = 0.008; Cramér’s V coefficient, 0.75). The size of the deletion was correlated in a statistically significant manner with the presence of oligodontia (p = 0.009; point-biserial correlation coefficient, 0.75). Conclusion: Certain oral manifestations prevalent in WHS can form part of the syndrome’s phenotypic variability. A number of the characteristics of WHS, such as psychomotor delay and epilepsy, are correlated with oral findings such as oligodontia and bruxism. Although most genotype-phenotype correlations are currently unknown, most of them seem to be associated with larger deletions, suggesting that some oral-facial candidate genes might be outside the critical WHS region, indicating that WHS is a contiguous gene syndrome. MDPI 2020-11-04 /pmc/articles/PMC7694380/ /pubmed/33158290 http://dx.doi.org/10.3390/jcm9113556 Text en © 2020 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Limeres, Jacobo
Serrano, Candela
De Nova, Joaquin Manuel
Silvestre-Rangil, Javier
Machuca, Guillermo
Maura, Isabel
Cruz Ruiz-Villandiego, Jose
Diz, Pedro
Blanco-Lago, Raquel
Nevado, Julian
Diniz-Freitas, Marcio
Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title_full Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title_fullStr Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title_full_unstemmed Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title_short Oral Manifestations of Wolf-Hirschhorn Syndrome: Genotype-Phenotype Correlation Analysis
title_sort oral manifestations of wolf-hirschhorn syndrome: genotype-phenotype correlation analysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7694380/
https://www.ncbi.nlm.nih.gov/pubmed/33158290
http://dx.doi.org/10.3390/jcm9113556
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