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The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors
Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
YJBM
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686787/ https://www.ncbi.nlm.nih.gov/pubmed/34970104 |
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author | Kyei-Barffour, Isaac Margetts, Miranda Vash-Margita, Alla Pelosi, Emanuele |
author_facet | Kyei-Barffour, Isaac Margetts, Miranda Vash-Margita, Alla Pelosi, Emanuele |
author_sort | Kyei-Barffour, Isaac |
collection | PubMed |
description | Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice. |
format | Online Article Text |
id | pubmed-8686787 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | YJBM |
record_format | MEDLINE/PubMed |
spelling | pubmed-86867872021-12-29 The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors Kyei-Barffour, Isaac Margetts, Miranda Vash-Margita, Alla Pelosi, Emanuele Yale J Biol Med Review Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder caused by Müllerian ducts dysgenesis affecting 1 in 5000 women with a typical 46,XX karyotype. The etiology of MRKH syndrome is complex and largely unexplained. Familial clustering suggests a genetic component and the spectrum of clinical presentations seems consistent with an inheritance pattern characterized by incomplete penetrance and variable expressivity. Mutations of several candidate genes have been proposed as possible causes based on genetic analyses of human patients and animal models. In addition, studies of monozygotic twins with discordant phenotypes suggest a role for epigenetic changes following potential exposure to environmental compounds. The spectrum of clinical presentations is consistent with intricate disruptions of shared developmental pathways or signals during early organogenesis. However, the lack of functional validation and translational studies have limited our understanding of the molecular mechanisms involved in this condition. The clinical management of affected women, including early diagnosis, genetic testing of MRKH syndrome, and the implementation of counseling strategies, is significantly impeded by these knowledge gaps. Here, we illustrate the embryonic development of tissues and organs affected by MRKH syndrome, highlighting key pathways that could be involved in its pathogenesis. In addition, we will explore the genetics of this condition, as well as the potential role of environmental factors, and discuss their implications to clinical practice. YJBM 2021-12-29 /pmc/articles/PMC8686787/ /pubmed/34970104 Text en Copyright ©2021, Yale Journal of Biology and Medicine https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons CC BY-NC license, which permits use, distribution, and reproduction in any medium, provided the original work is properly cited. You may not use the material for commercial purposes. |
spellingShingle | Review Kyei-Barffour, Isaac Margetts, Miranda Vash-Margita, Alla Pelosi, Emanuele The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser Syndrome: Genetics and Environmental Factors |
title | The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors |
title_full | The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors |
title_fullStr | The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors |
title_full_unstemmed | The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors |
title_short | The Embryological Landscape of Mayer-Rokitansky-Kuster-Hauser
Syndrome: Genetics and Environmental Factors |
title_sort | embryological landscape of mayer-rokitansky-kuster-hauser
syndrome: genetics and environmental factors |
topic | Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8686787/ https://www.ncbi.nlm.nih.gov/pubmed/34970104 |
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