Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case
Abstract Background In this study we aimed to describe the morphological and pathogenetic differences between tracheal agenesis and tracheal atresia, which are not clearly distinguished from each other in the literature, and to contribute thereby to the understanding and management of these conditio...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-024-03106-z |
| _version_ | 1827315767936286720 |
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| author | Mateja Pfeifer Helga Rehder Maria Gerykova Bujalkova Christine Bartsch Barbara Fritz Cordula Knopp Björn Beckers Frank Dohle Matthias Meyer-Wittkopf Roland Axt-Fliedner Alexander V. Beribisky Manuel Hofer Franco Laccone Katharina Schoner |
| author_facet | Mateja Pfeifer Helga Rehder Maria Gerykova Bujalkova Christine Bartsch Barbara Fritz Cordula Knopp Björn Beckers Frank Dohle Matthias Meyer-Wittkopf Roland Axt-Fliedner Alexander V. Beribisky Manuel Hofer Franco Laccone Katharina Schoner |
| author_sort | Mateja Pfeifer |
| collection | DOAJ |
| description | Abstract Background In this study we aimed to describe the morphological and pathogenetic differences between tracheal agenesis and tracheal atresia, which are not clearly distinguished from each other in the literature, and to contribute thereby to the understanding and management of these conditions. Both tracheal agenesis and tracheal atresia represent rare disorders of still unknown aetiology that cannot be detected by prenatal ultrasound. If the affected foetuses survive until birth these conditions result in respiratory failure and in futile attempts to rescue the infant’s life. Results Autopsies and genetic analyses, including singleton or trio exome sequencing, were performed on five neonates/foetuses with tracheal agenesis and three foetuses with tracheal atresia. Tracheal agenesis was characterized by absence of the sublaryngeal trachea and presence of a bronchooesophageal fistula and by pulmonary isomerism and occurred as an isolated malformation complex or as part of a VACTERL association. Special findings were an additional so-called ‘pig bronchus’ and a first case of tracheal agenesis with sirenomelia. Tracheal atresia presenting with partial obliteration of its lumen and persistence of a fibromuscular streak resulted in CHAOS. This condition was associated with normal lung lobulation and single, non-VACTERL type malformations. Trio ES revealed a novel variant of MAPK11 in one tracheal agenesis case. Its involvement in tracheooesophageal malformation is herein discussed, but remains hypothetical. Conclusion Tracheal agenesis and tracheal atresia represent different disease entities in terms of morphology, pathogenesis and accompanying anomalies due to a primary developmental and secondary disruptive possibly vascular disturbance, respectively. |
| first_indexed | 2024-04-24T23:02:51Z |
| format | Article |
| id | doaj.art-a27bc7de37c240fbb01c3dfa427cba1f |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-04-24T23:02:51Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-a27bc7de37c240fbb01c3dfa427cba1f2024-03-17T12:38:06ZengBMCOrphanet Journal of Rare Diseases1750-11722024-03-0119111110.1186/s13023-024-03106-zTracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one caseMateja Pfeifer0Helga Rehder1Maria Gerykova Bujalkova2Christine Bartsch3Barbara Fritz4Cordula Knopp5Björn Beckers6Frank Dohle7Matthias Meyer-Wittkopf8Roland Axt-Fliedner9Alexander V. Beribisky10Manuel Hofer11Franco Laccone12Katharina Schoner13Institute of Medical Genetics, Medical University of ViennaInstitute of Medical Genetics, Medical University of ViennaInstitute of Medical Genetics, Medical University of ViennaInstitute of Forensic Medicine, University of ZürichInstitute of Human Genetics, Philipps-University of MarburgInstitute of Human Genetics, RWTHChildren’s Hospital St. LouiseDepartment of Pediatrics, Children’s Center Bethel, University BielefeldDepartment of Gynecology and Obstetrics, University Clinic OldenburgDivision of Prenatal Medicine and Fetal Therapy, University Hospital GiessenInstitute of Medical Genetics, Medical University of ViennaInstitute of Medical Genetics, Medical University of ViennaInstitute of Medical Genetics, Medical University of ViennaInstitute of Pathology, Fetal Pathology, Philipps-University of MarburgAbstract Background In this study we aimed to describe the morphological and pathogenetic differences between tracheal agenesis and tracheal atresia, which are not clearly distinguished from each other in the literature, and to contribute thereby to the understanding and management of these conditions. Both tracheal agenesis and tracheal atresia represent rare disorders of still unknown aetiology that cannot be detected by prenatal ultrasound. If the affected foetuses survive until birth these conditions result in respiratory failure and in futile attempts to rescue the infant’s life. Results Autopsies and genetic analyses, including singleton or trio exome sequencing, were performed on five neonates/foetuses with tracheal agenesis and three foetuses with tracheal atresia. Tracheal agenesis was characterized by absence of the sublaryngeal trachea and presence of a bronchooesophageal fistula and by pulmonary isomerism and occurred as an isolated malformation complex or as part of a VACTERL association. Special findings were an additional so-called ‘pig bronchus’ and a first case of tracheal agenesis with sirenomelia. Tracheal atresia presenting with partial obliteration of its lumen and persistence of a fibromuscular streak resulted in CHAOS. This condition was associated with normal lung lobulation and single, non-VACTERL type malformations. Trio ES revealed a novel variant of MAPK11 in one tracheal agenesis case. Its involvement in tracheooesophageal malformation is herein discussed, but remains hypothetical. Conclusion Tracheal agenesis and tracheal atresia represent different disease entities in terms of morphology, pathogenesis and accompanying anomalies due to a primary developmental and secondary disruptive possibly vascular disturbance, respectively.https://doi.org/10.1186/s13023-024-03106-zTracheal agenesisTracheal atresiaCongenital high airway obstruction sequence (CHAOS)VACTERL associationSirenomeliaMAPK11 variant |
| spellingShingle | Mateja Pfeifer Helga Rehder Maria Gerykova Bujalkova Christine Bartsch Barbara Fritz Cordula Knopp Björn Beckers Frank Dohle Matthias Meyer-Wittkopf Roland Axt-Fliedner Alexander V. Beribisky Manuel Hofer Franco Laccone Katharina Schoner Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case Orphanet Journal of Rare Diseases Tracheal agenesis Tracheal atresia Congenital high airway obstruction sequence (CHAOS) VACTERL association Sirenomelia MAPK11 variant |
| title | Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case |
| title_full | Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case |
| title_fullStr | Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case |
| title_full_unstemmed | Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case |
| title_short | Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case |
| title_sort | tracheal agenesis versus tracheal atresia anatomical conditions pathomechanisms and causes with a possible link to a novel mapk11 variant in one case |
| topic | Tracheal agenesis Tracheal atresia Congenital high airway obstruction sequence (CHAOS) VACTERL association Sirenomelia MAPK11 variant |
| url | https://doi.org/10.1186/s13023-024-03106-z |
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