Tracheal Agenesis Research Articles

A Case Series On Tracheal Atresia

Background: Agenesis, aplasia or atresia of the trachea is a rare congenital anomaly that to date seems to be incompatible with life. Tracheal atresia is a congenital absence of a normal passage that does not imply a particular length of involvement. Tracheal atresia encompasses cases of agenesis (total absence of trachea) as well as varying lengths of tracheal mal-development1 . We describe here 3 cases of tracheal agenesis. Materials and Methods: It is a descriptive case series done with three neonates in tertiary care teaching hospital in Department of Paediatrics. Conclusion: tracheal atresia is a rare anomaly and clinicians need to be aware of this condition to provide adequate supportive management at the time of delivery and subsequently

Rare type of tracheal agenesis: Unexpected presentation and immediate consideration of emergent esophageal intubation in neonatal resuscitation program. Case reports and review of the literature.

Tracheal agenesis, or tracheal atresia, is a rare congenital anomaly. The presence of a tracheoesophageal fistula (TEF) can help with breathing for newborns with tracheal agenesis. In this article, we presented three unique cases and outcomes of neonates with tracheal agenesis along with a review of the literature. This study consisted of a single center case series followed by a review of literature. Case reports were generated using both written and electronic medical records from a single hospital. We summarized three unique cases and outcomes of neonates with tracheal agenesis and performed a review of the literature. We identified three cases of tracheal agenesis presented with severe cyanosis without spontaneous crying upon birth. Experienced pediatricians attempted to intubate the babies but were unsuccessful. Endotracheal tubes were subsequently either accidentally or purposely placed into the esophagus, and oxygen saturation levels improved. This suggested tracheal agenesis with TEF. Two cases underwent surgical intervention after resuscitation with esophageal intubation. Esophageal intubation may be a life-sustaining ventilation support for patients with tracheal agenesis and TEF at initial resuscitation. Clinicians should suspect tracheal agenesis when a newborn presents with severe cyanosis and voiceless crying upon birth, and esophageal intubation should be immediately attempted.

Tracheal agenesis versus tracheal atresia: anatomical conditions, pathomechanisms and causes with a possible link to a novel MAPK11 variant in one case

BackgroundIn 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.ResultsAutopsies 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.ConclusionTracheal 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.

Floyd Type II Congenital Tracheal Agenesis in a Preterm Neonate: A Rare Case Report

Tracheal agenesis is a rare and life-threatening airway malformation, and currently, there is no curative treatment available. The described case involves a preterm male newborn at 30 weeks of gestational age who could not be intubated during resuscitation, despite multiple attempts. However, the baby could be ventilated after oesophageal intubation. Tracheal stenosis/ atresia was suspected, and airway evaluation was performed using a thin, flexible fiberoptic bronchoscope. No tracheal opening could be identified, and upon introducing the bronchoscope into the oesophagus, a triluminal opening was found, through which the scope could not be further navigated. To further delineate the anatomy, a Contrast-enhanced Computed Tomography (CECT) thorax was performed, revealing the absence of a tracheal lumen and the communication of both bronchi at the carina with the oesophagus. Unfortunately, the baby succumbed to the illness after three days. Tracheal agenesis is an anatomical malformation that typically presents as respiratory distress and the absence of an audible cry at birth. Attempts to establish a definite airway are unsuccessful, which may result in early neonatal death. Oesophageal intubation may temporarily establish ventilation until palliative surgery is performed.

Stumbled across a rare entity tracheal agenesis - A lesson learned.

Stumbled across a rare entity tracheal agenesis - A lesson learned.

Successful application of the innovation process to a case of Floyd Type I tracheal agenesis

BackgroundInnovation is broadly defined as the act of introducing a new product, idea, or process. The field of surgery is built upon innovation, revolutionizing technology, science, and tools to improve patient care. While most innovative solutions are aimed at problems with a significant patient population, the process can also be used on orphan pathologies without obvious solutions. We present a case of tracheal agenesis, a rare congenital anomaly with an overwhelming mortality and few good treatment options, that benefited from the innovation process and achieved survival with no ventilator dependence at three years of age. MethodsUtilizing the framework of the innovation process akin to the Stanford Biodesign Program, 1) the parameters of the clinical problem were identified, 2) previous solutions and existing technologies were analyzed, newly invented solutions were brainstormed, and value analysis of the possible solutions were carried out using crowd wisdom, and 3) the selected solution was prototyped and tested using 3D modeling, iterative testing on 3D prints of actual-sized patient parts, and eventual implementation in the patient after regulatory clearance. ResultsA 3D-printed external bioresorbable splint was chosen as the solution. Our patient underwent airway reconstruction with “trachealization of the esophagus”: esophageotracheal fistula resection, esophagotracheoplasty, and placement of a 3D-printed polycaprolactone (PCL) stent for external esophageal airway support at five months of age. ConclusionsThe innovation process provided our team with the guidance and imperative steps necessary to develop an innovative device for the successful management of an infant survivor with Floyd Type I tracheal agenesis. Article summaryWe present a case of tracheal agenesis, a rare congenital anomaly with an overwhelming mortality and few good treatment options, that benefited from the innovation process and achieved survival with no ventilator dependence at three years of age.The importance of this report is to reveal how the innovation process, which is typically used for problems with significant patient population, can also be used on orphan pathologies without obvious solutions.

Development of a Lung Vacancy Mouse Model through CRISPR/Cas9-Mediated Deletion of Thyroid Transcription Factor 1 Exon 2

A developmental niche vacancy in host embryos is necessary for stem cell complementation-based organ regeneration (SCOG). Thyroid transcription factor 1 (TTF-1) is a tissue-specific transcription factor that regulates the embryonic development and differentiation of the thyroid and, more importantly, lungs; thus, it has been considered as a master gene to knockout in order to develop a lung vacancy host. TTF-1 knockout mice were originally produced by inserting a stop codon in Exon 3 of the gene (E3stop) through embryonic stem cell-based homologous recombination. The main problems of utilizing E3stop host embryos for lung SCOG are that these animals all have a tracheoesophageal fistula (TEF), which cannot be corrected by donor stem cells, and most of them have monolateral sac-like lungs. To improve the mouse model towards achieving SCOG-based lung generation, in this project, we used the CRISPR/Cas9 tool to remove Exon 2 of the gene by zygote microinjection and successfully produced TTF-1 knockout (E2del) mice. Similar to E3stop, E2del mice are birth-lethal due to retarded lung development with sac-like lungs and only a rudimentary bronchial tree, increased basal cells but without alveolar type II cells and blood vessels, and abnormal thyroid development. Unlike E3stop, 57% of the E2del embryos presented type I tracheal agenesis (TA, a kind of human congenital malformation) with a shortened trachea and clear separations of the trachea and esophagus, while the remaining 43% had TEF. Furthermore, all the E2del mice had bilateral sac-like lungs. Both TA and bilateral sac-like lungs are preferred in SCOG. Our work presents a new strategy for producing SCOG host embryos that may be useful for lung regeneration.

Anatomy and embryology of tracheo-esophageal fistula

Anomalies in tracheo-esophageal development result in a spectrum of congenital malformations ranging from, most commonly, esophageal atresia with or without trachea-esophageal fistula (EA+/-TEF) to esophageal web, duplication, stricture, tracheomalacia and tracheal agenesis. Despite the relative frequency of EA, however, the underlying etiology remains unknown and is likely due to a combination of genetic, epigenetic and environmental factors. In recent years, animal models have dramatically increased our understanding of the molecular and morphological processes involved in normal esophageal development during the key stages of anterior-posterior regionalization, dorsal-ventral patterning and morphogenic separation. Moreover, the use of animal models in conjunction with increasingly advanced techniques such as genomic sequencing, sophisticated live imaging studies and organoid models have more recently cast light on potential mechanisms involved in EA pathogenesis. This article aims to unravel some of the mysteries behind the anatomy and embryology of EA whilst providing insights into future directions for research.

The challenging airway: Tracheal agenesis in the newborn.

A preterm female presented with severe respiratory distress in the delivery room and was found to have tracheal agenesis with a tracheoesophageal fistula and a congenital heart defect. Tracheal agenesis is uncommon and is often associated with other congenital abnormalities. Although there are surgical options for repair, mortality remains high.

Esophageal Reconstruction Using the Stomach for Tracheal Agenesis and Complicated Long-gap Esophageal Atresia

Esophageal Reconstruction Using the Stomach for Tracheal Agenesis and Complicated Long-gap Esophageal Atresia

Congenital anomalies of the large intrathoracic airways

Congenital lung lesions are numerous but rare in individual clinical practice. They do require close multidisciplinary collaboration between health care professionals. This educational review will focus on the pathophysiology, clinical manifestations, surgical approaches, and anesthetic management of congenital anomalies of the large intrathoracic airways: congenital tracheal stenosis, tracheal agenesis, tracheal diverticulum, bronchial anomalies (tracheal, esophageal, or bridging bronchus), congenital lung malformations, lung sequestrations and Scimitar syndrome, lobar emphysema, Williams-Campbell syndrome, and pleuropulmonary blastoma. In addition, this review will illustrate common pitfalls and challenges related to the anesthesia management with emphasis on ventilation and correct endotracheal tube positioning.

Congenital airway anomalies

Congenital airway anomalies (CAA) include a variety of conditions that cause respiratory distress in neonates and infants. These malformations occur at various anatomic levels and manifest in a wide spectrum of airway symptoms, with presentation significantly influenced by the level at which obstruction occurs as well as by the severity of obstruction. The prevalence of congenital airway malformations has been estimated to range between 0.2 and 1 in 10,000 live births. The most frequent CAA are laryngomalacia, bilateral vocal cord paralysis, subglottic stenosis, laryngeal webs, subglottic hemangioma, tracheomalacia, congenital tracheal stenosis, laryngotracheal cleft, and tracheal agenesis.

Molecular crosstalk in tracheal development and its recurrence in adult tissue regeneration.

The trachea is a rigid air duct with some mobility, which comprises the upper region of the respiratory tract and delivers inhaled air to alveoli for gas exchange. During development, the tracheal primordium is first established at the ventral anterior foregut by interactions between the epithelium and mesenchyme through various signaling pathways, such as Wnt, Bmp, retinoic acid, Shh, and Fgf, and then segregates from digestive organs. Abnormalities in this crosstalk result in lethal congenital diseases, such as tracheal agenesis. Interestingly, these molecular mechanisms also play roles in tissue regeneration in adulthood, although it remains less understood compared with their roles in embryonic development. In this review, we discuss cellular and molecular mechanisms of trachea development that regulate the morphogenesis of this simple tubular structure and identities of individual differentiated cells. We also discuss how the facultative regeneration capacity of the epithelium is established during development and maintained in adulthood.

Tracheal agenesis: a rare congenital disorder

Tracheal agenesis is a severe congenital disorder with often an emergency presentation. There is acomplete or partial absence of the trachea below the larynx, with the presence or absence of atracheoesophageal fistula. It is a rare differential diagnosis of postnatal respiratory distress and theobstetrician or neonatologist will regularly be surprised by this malformation. The etiology ofTracheal atresia is unknown, therapeutic options are limited thus making this condition a usuallyfatal disorder. In most cases, congenital anomalies of the heart, digestive tract or GUT are present.The main signs are respiratory distress and cyanosis, inability to vocalize and impossible trachealintubation. Isolated tracheal agenesis without any malformation is very rare. Here we report a caseof a preterm neonate born at 33 weeks gestation with tracheal agenesis with no other associatedmalformation. In most cases, the seldom deformation, tracheal agenesis does not get recognizedbefore the child is born.

The long-term outcome of tracheal agenesis following reconstruction of the airway and alimentary tract

Abstract We herein report the 14-year-follow-up of a patient with tracheal agenesis (TA) after reconstruction of the airway and alimentary tract. A 2536-g female infant was diagnosed with TA of Floyd’-s type 1. Her condition was stabilized by the direct insertion of a ready-made endotracheal tube into a tracheo-esophageal fistula, after birth. At seven days old, she underwent esophageal transection, gastrostomy, and cervical esophageal division, and distal cervical esophagostomy was created as a neo-trachealized esophagus. During early infancy, a ready-made endotracheal tube had been used as an internal esophageal stent. At 7 months old, a custom-made long tracheostomy tube was substituted, which was revised according to her growth, and her respiratory condition became stable thereafter. At 7 years old, her alimentary tract was reconstructed using a gastric tube, and the post-operative course was uneventful; she eventually achieved oral intake 5 years after this surgery. She is now 14 years and 5 months old, and shows a substandard height and weight, with a slower-than-normal neurologic and physiologic development for her age. As a result, she currently attends a special-needs school. We also reviewed six other long-term survival cases to date. The present report seems to describe the longest-term outcome of a patient with TA.

Tracheal anomalies associated with Down syndrome: A systematic review.

IntroductionAirway anomalies are accountable for a substantial part of morbidity and mortality in children with Down syndrome (DS). Although tracheal anomalies occur more often in DS children, a structured overview on the topic is lacking. We systematically reviewed the characteristics of tracheal anomalies in DS children.MethodsA MEDLINE and EMBASE search for DS and tracheal anomalies was performed. Tracheal anomalies included tracheal stenosis, complete tracheal ring deformity (CTRD), tracheal bronchus, tracheomalacia, tracheal web, tracheal agenesis or atresia, laryngotracheoesophageal cleft type 3 or 4, trachea sleeve, and absent tracheal rings.ResultsFifty‐nine articles were included. The trachea of DS children is significantly smaller than non‐DS children. Tracheomalacia and tracheal bronchus are seen significantly more often in DS children. Furthermore, tracheal stenosis, CTRD, and tracheal compression by vascular structures are seen regularly in children with DS. These findings are reflected by the significantly higher frequency of tracheostomy and tracheoplasty performed in DS children.ConclusionIn children with DS, tracheal anomalies occur more frequently and tracheal surgery is performed more frequently than in non‐DS children. When complaints indicative of tracheal airway obstruction like biphasic stridor, dyspnea, or wheezing are present in children with DS, diagnostic rigid laryngotracheobronchoscopy with special attention to the trachea is indicated. Furthermore, imaging studies (computed tomography, magnetic resonance imaging, and ultrasound) play an important role in the workup of DS children with airway symptoms. Management depends on the type, number, and extent of tracheal anomalies. Surgical treatment seems to be the mainstay in severe cases.

Редкое наблюдение агенезии трахеи у недоношенного ребенка на фоне множественных пороков развития

We report a case of tracheal agenesis complicated by multiple malformations of the respiratory, digestive, and urinary tracts in a preterm baby who required specialized emergency care rom the first minutes of its life and survived for 53 days. The aim of this case report is to provide a detailed description of the diagnosis and treatment stages in this patient and demonstrate possible errors and tactical approaches to surgical correction of tracheal agenesis. Because of the fact that this disorder is exceedingly rare and was combined with other malformations, its main symptom, pronounced respiratory insufficiency, is not usually considered as a result of upper respiratory tract lesions. The majority of patients are diagnosed post-mortem. Moreover, the vascular graft forming the frame of the newly created trachea allows stable independent breathing for quite a long time in patients with tracheal agenesis. Key words: tracheal agenesis, respiratory failure, multiple malformations, preterm newborn, vascular graft

Bidirectional Wnt signaling between endoderm and mesoderm confers tracheal identity in mouse and human cells

The periodic cartilage and smooth muscle structures in mammalian trachea are derived from tracheal mesoderm, and tracheal malformations result in serious respiratory defects in neonates. Here we show that canonical Wnt signaling in mesoderm is critical to confer trachea mesenchymal identity in human and mouse. At the initiation of tracheal development, endoderm begins to express Nkx2.1, and then mesoderm expresses the Tbx4 gene. Loss of β-catenin in fetal mouse mesoderm causes loss of Tbx4+ tracheal mesoderm and tracheal cartilage agenesis. The mesenchymal Tbx4 expression relies on endodermal Wnt activation and Wnt ligand secretion but is independent of known Nkx2.1-mediated respiratory development, suggesting that bidirectional Wnt signaling between endoderm and mesoderm promotes trachea development. Activating Wnt, Bmp signaling in mouse embryonic stem cell (ESC)-derived lateral plate mesoderm (LPM) generates tracheal mesoderm containing chondrocytes and smooth muscle cells. For human ESC-derived LPM, SHH activation is required along with WNT to generate proper tracheal mesoderm. Together, these findings may contribute to developing applications for human tracheal tissue repair.

The diagnostic role of multidetector computed tomography in congenital tracheal agenesis

The diagnostic role of multidetector computed tomography in congenital tracheal agenesis

Tracheal agenesis: A rare but fatal congenital anomaly

In this report we describe a newborn with a rare case of Type II tracheal agenesis and bronchoesophageal fistula. Polyhydramnios and suspected esophageal atresia were identified during routine pre-natal ultrasound screening. Upon delivery, rigid bronchoscopy, esophagoscopy, and intraoperative fluoroscopy were performed, where both bronchi and the carina showed unusual horizontal orientation making it difficult to identify the fistula. However, a post mortem CT confirmed the diagnosis of an isolated Type II tracheal agenesis with bronchoesophageal fistula.