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Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation

Background Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-β) pa...

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Autores principales: Jani, Priyam, Nguyen, Quynh C, Almpani, Konstantinia, Keyvanfar, Cyrus, Mishra, Rashmi, Liberton, Denise, Orzechowski, Pamela, Frischmeyer-Guerrerio, Pamela A, Duverger, Olivier, Lee, Janice S
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BMJ Publishing Group 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525783/
https://www.ncbi.nlm.nih.gov/pubmed/32152251
http://dx.doi.org/10.1136/jmedgenet-2019-106678
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author Jani, Priyam
Nguyen, Quynh C
Almpani, Konstantinia
Keyvanfar, Cyrus
Mishra, Rashmi
Liberton, Denise
Orzechowski, Pamela
Frischmeyer-Guerrerio, Pamela A
Duverger, Olivier
Lee, Janice S
author_facet Jani, Priyam
Nguyen, Quynh C
Almpani, Konstantinia
Keyvanfar, Cyrus
Mishra, Rashmi
Liberton, Denise
Orzechowski, Pamela
Frischmeyer-Guerrerio, Pamela A
Duverger, Olivier
Lee, Janice S
author_sort Jani, Priyam
collection PubMed
description Background Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-β) pathway, LDS is presently classified into six subtypes. Methods We present the oro-dental features of a cohort of 40 patients with LDS from five subtypes. Results The most common oro-dental manifestations were the presence of a high-arched and narrow palate, and enamel defects. Other common characteristics included bifid uvula, submucous cleft palate, malocclusion, dental crowding and delayed eruption of permanent teeth. Both deciduous and permanent teeth had enamel defects in some individuals. We established a grading system to measure the severity of enamel defects, and we determined that the severity of the enamel anomalies in LDS is subtype-dependent. In specific, patients with TGF-β receptor II mutations (LDS2) presented with the most severe enamel defects, followed by patients with TGF-β receptor I mutations (LDS1). LDS2 patients had higher frequency of oro-dental deformities in general. Across all five subtypes, as well as within each subtype, enamel defects exhibited incomplete penetrance and variable expression, which is not associated with the location of the gene mutations. Conclusion This study describes, in detail, the oro-dental manifestations in a cohort of LDS, and we conclude that LDS2 has the most severely affected phenotype. This extensive characterisation, as well as some identified distinguishing features can significantly aid dental and medical care providers in the diagnosis and clinical management of patients with this rare connective tissue disorder.
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spelling pubmed-75257832020-10-19 Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation Jani, Priyam Nguyen, Quynh C Almpani, Konstantinia Keyvanfar, Cyrus Mishra, Rashmi Liberton, Denise Orzechowski, Pamela Frischmeyer-Guerrerio, Pamela A Duverger, Olivier Lee, Janice S J Med Genet Developmental Defects Background Loeys-Dietz syndrome (LDS), an autosomal dominant rare connective tissue disorder, has multisystemic manifestations, characterised by vascular tortuosity, aneurysms and craniofacial manifestations. Based on the associated gene mutations along the transforming growth factor-beta (TGF-β) pathway, LDS is presently classified into six subtypes. Methods We present the oro-dental features of a cohort of 40 patients with LDS from five subtypes. Results The most common oro-dental manifestations were the presence of a high-arched and narrow palate, and enamel defects. Other common characteristics included bifid uvula, submucous cleft palate, malocclusion, dental crowding and delayed eruption of permanent teeth. Both deciduous and permanent teeth had enamel defects in some individuals. We established a grading system to measure the severity of enamel defects, and we determined that the severity of the enamel anomalies in LDS is subtype-dependent. In specific, patients with TGF-β receptor II mutations (LDS2) presented with the most severe enamel defects, followed by patients with TGF-β receptor I mutations (LDS1). LDS2 patients had higher frequency of oro-dental deformities in general. Across all five subtypes, as well as within each subtype, enamel defects exhibited incomplete penetrance and variable expression, which is not associated with the location of the gene mutations. Conclusion This study describes, in detail, the oro-dental manifestations in a cohort of LDS, and we conclude that LDS2 has the most severely affected phenotype. This extensive characterisation, as well as some identified distinguishing features can significantly aid dental and medical care providers in the diagnosis and clinical management of patients with this rare connective tissue disorder. BMJ Publishing Group 2020-10 2020-03-08 /pmc/articles/PMC7525783/ /pubmed/32152251 http://dx.doi.org/10.1136/jmedgenet-2019-106678 Text en © Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ. http://creativecommons.org/licenses/by-nc/4.0/ http://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.
spellingShingle Developmental Defects
Jani, Priyam
Nguyen, Quynh C
Almpani, Konstantinia
Keyvanfar, Cyrus
Mishra, Rashmi
Liberton, Denise
Orzechowski, Pamela
Frischmeyer-Guerrerio, Pamela A
Duverger, Olivier
Lee, Janice S
Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title_full Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title_fullStr Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title_full_unstemmed Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title_short Severity of oro-dental anomalies in Loeys-Dietz syndrome segregates by gene mutation
title_sort severity of oro-dental anomalies in loeys-dietz syndrome segregates by gene mutation
topic Developmental Defects
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7525783/
https://www.ncbi.nlm.nih.gov/pubmed/32152251
http://dx.doi.org/10.1136/jmedgenet-2019-106678
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