Tracheal agenesis

Last updated
Tracheal agenesis
Other namesCongenital tracheal agenesis [1]
Complications Other congenital malformations
CausesUnknown

Tracheal agenesis (also known as tracheal atresia) is a rare birth defect [2] with a prevalence of less than 1 in 50,000 [3] in which the trachea fails to develop, resulting in an impaired communication between the larynx and the alveoli of the lungs. [1] Although the defect is normally fatal, [3] [4] occasional cases have been reported of long-term survival following surgical intervention. [4] [5]

Contents

The disease was first described in 1900 by Payne. [6] To this date, it is estimated that about 200 cases have been reported and published worldwide. Several types of the disease have been described and the slight anatomical variations have resulted in the establishment of different classification systems. [7] There are three main types of tracheal agenesis, designated Types I, II and III. [3]

In 2013, a South Korean child, Hannah Warren, born with tracheal agenesis, [8] was successfully treated at Children's Hospital of Illinois, after having been kept alive in an intensive care unit for the first two and a half years of her life. An artificially created trachea was implanted, that had been created by tissue engineering, by using a nanofiber mesh, coated with her own stem cells. [8] [9] Although the transplant was successful, she died three months later from other health issues. [10]

The disease has been more frequently observed in males than in females, at a ratio of 2:1. [3]

Signs and symptoms

Observable signs and symptoms of the disease differ depending on whether the observation in done in utero or after parturition. Only the signs and symptoms of the embryo are described, due to the lack of research in maternal symptoms.[ citation needed ]

In utero

Incidence of congenital malformations associated with tracheal agenesis. Results were obtained from a total of 32 individual case studies. Tracheal agenesis - Incidence of congenital malformations.jpg
Incidence of congenital malformations associated with tracheal agenesis. Results were obtained from a total of 32 individual case studies.

The classic in-utero symptoms of tracheal agenesis are an absence of the trachea leading to congenital high airway obstruction syndrome, [12] [13] lung distention, polyhydramnios, heart malformations, heart displacement and hydrops fetalis. [1] [12] [14] [15] Other congenital malformations such as genitourinary, gastrointestinal and musculoskeletal anomalies are common and occur in 80% of the reported cases. [16] [11]

Tracheal agenesis may lead to a distention of the foetus’ lung due to a build-up of pulmonary fluid within them. In this case, ultrasound scans show bilaterally enlarged and homogeneously echogenic lungs as well as the inversion of both hemidiaphragms. [14] Although lung distention has been described as a classic symptom, hypoplasia or complete aplasia of the lungs can also occur, in an estimated 26% of cases. [1] [15] In some cases, normal lung development was also reported in neonates with tracheal agenesis. [16]

The abnormal development of the foetus’ lungs leads to cardiovascular abnormalities. Distention of the lungs results in a compressed and displaced heart, hindering the normal growth and development of the organ. Depending on the severity of the compression of the heart, normal venous return to the organ would correspondingly be hindered, resulting in a condition known as hydrops fetalis (also known as fetalis ascites), [14] in which oedema form in the developing foetus. Hydrops fetalis can be observed in utero via ultrasound scan.

Polyhydramnios occurs in embryos presenting with a tracheoesophageal fistula as the liquid produced by the lungs supposedly pass to the stomach, in the amniotic fluid. [17]

At birth

More than half of the recorded cases of tracheal agenesis have led to premature deliveries [15] [16] and in almost all reported cases, infants die shortly after birth due to lack of oxygenation. Neonates with tracheal agenesis present with symptoms characteristic to congenital high airway obstruction syndrome with no audible cry after birth, respiratory insufficiency, respiratory distress and cyanosis. [16] [17] No trachea is palpable below the cricoid cartilage.

Causes

The exact causes of tracheal agenesis remain unknown. Different embryological theories have arisen to explain the congenital development of the disease.

Embryological causes

The relative similarities between the different subtypes of the disease suggest that there is a common stage at which the development is hindered.

In normal embryogenesis, the trachea differentiates from the foregut during the fourth week of gestation. The respiratory diverticulum, a ventral projection formed from the foregut, appears. Eventually, the tracheoesophageal ridges will fuse to form a septum. The laryngotracheal tube will then fully separate from the foregut. [18] Two primary bronchial buds form at the end of the tube, which then elongates to form the trachea. The buds then branch to form the bronchi, lungs and alveolar tissue. The development of the respiratory tract is closely associated to that of the oesophagus. [18] Both organs regulate each other’s growth via molecular interactions.

In tracheal agenesis, a delay in the development of the primary bronchial buds causes a transient arrest in the growth of the laryngotracheal tube, hindering the normal development of the trachea. [3] The failure of the lung buds to develop from the primitive foregut leads to tracheoesophageal malformations. [19] The development of the buds occurs after the elongation of the oesophagus, causing a dissociation in the growth of the two organs. Due to this dissociation, the buds directly develop to form the lungs, without forming the trachea, resulting in tracheal agenesis. [20] Different degrees of this malformation result in different types of tracheal agenesis.

Genetic determinants

No clear genetic pattern or karyotype has been established to support the development of tracheal agenesis. The genes that have been postulated to influence the development of the disease are all associated to the congenital development of the lungs, trachea and oesophagus. These are BMP-4, BMPR1A and BMPR1B, Gli2 and Gli3, sonic hedgehog and NK2 homeobox 1. [21] [22] [23] [24] It is highly likely that tracheal agenesis results from the mutation of several of these genes. [12]

BMP-4  is an important signalling molecule in the early development of the embryo. BMP-4 null mutations in the foregut endoderm and in its surrounding mesoderm results in atresia of the trachea and under developed lungs. [21] The Bmp family restricts the site of formation of lung buds as well as to induce cell proliferation via the suppression of Sox2. [22]

Gli2 and Gli3 null mutations were also found to result in delayed lung, tracheal and oesophageal development. [22] The two signalling molecules are implicated in the mediation of Sonic hedgehog signalling, which regulates the proliferation and differentiation of the oesophagus, trachea and lungs. [23]

In mice, NK2 homeobox 1 null mutation results in a significantly shorter trachea, connected to the oesophagus via a tracheoesophageal fistula. In embryos with a homozygous mutated NK2 homeobox 1 locus, the tracheoesophageal ridges fail to fuse and form a septum. [24]

Diagnosis

The diagnosis of the disease is dependent on observable signs and symptoms and on the stage of gestation. There are two ways to diagnose tracheal agenesis: early in utero, or later at birth. Recognisable clinical patterns are associated with tracheal agenesis.

Most commonly, the in-utero diagnosis of the disease requires using radiography and ultrasound scans.

At birth, the diagnosis is suspected clinically through the observations of characteristic signs and symptoms of the disease. Tracheal agenesis should be suspected when tracheal intubation is impossible. The confirmation of the diagnosis relies on results of endoscopic laryngoscopies and oesophagoscopies at birth. [15] X-ray studies are necessary to determine the class and the severity of the disease. CT scans remain an option to provide more information if required. [15]

Classification

Tracheal agenesis is classified according to anatomical subtypes. Different classifications exist but the universally accepted one, by Floyd and colleagues in 1962, distinguishes three anatomical subtypes: type I, II and III. [7]

Type I

Type I is described as tracheal atresia, rather than tracheal agenesis. The trachea is absent proximally but there remains a short normal segment of the distal trachea. A tracheoesophageal fistula links the distal segment of the proto trachea to the oesophagus. It is estimated that 13% of cases of the disease are of type I. [2]

Type II

Type II tracheal agenesis is the most common form of the disease, estimated to appear in 60% of cases. [2] Type II is characterised by a complete absence of the trachea. The bronchi are normal and fuse at the carina. In most cases, the oesophagus and the carina are joined by a fistula.

Type III

In type III tracheal agenesis, the trachea is completely absent and the bronchi develop individually, originating from the oesophagus directly and without joining at the carina. No tracheoesophageal fistula is present in this case as the trachea is completely absent. It is estimated that 27% of all cases are type III. [2]

Other classifications

In 1979, Faro described seven types of tracheal agenesis (A-G). [25] This classification system differs from Floyd’s early propositions as it encompasses a more detailed description of the disease, including the surrounding organs such as the larynx and the lungs. The importance of this more detailed classification system is that the presence of surrounding organs, such as the larynx, might alter the observed symptoms of the traditionally defined tracheal agenesis. For example, neonates with a larynx might emit a faint cry at birth, while those with complete agenesis of the trachea and of the larynx will not. Acknowledging these different anatomical subtypes allows for a more comprehensive diagnosis and better management of the disease.

Faro type A describes a total pulmonary agenesis, in which none of the respiratory organs are present. Type B is comparable to Floyd’s type III and describes complete agenesis of the trachea, with no joining of the bronchi. Faro type C describes total agenesis of the trachea with normal bronchi fusing at the carina. A tracheoesophageal fistula is present and links the carina to the oesophagus. In Faro type D, the larynx is joined to the distal trachea and a tracheoesophageal fistula links the carina to the oesophagus. Faro type E is comparable to Floyd’s type I, as the distal trachea is present and joined to the oesophagus via a fistula. Faro type F describes the proximal absence of the trachea but the normal presence of the distal trachea. In this case, the trachea is not attached to the oesophagus. In Faro type G, a segment of the trachea is absent, defining it as partial tracheal agenesis.

Management

In patients with tracheal agenesis, surgical correction is required to allow for a relatively temporary survival of the neonate. [26] Tracheal intubation is proven to be impossible in almost all cases. In most cases, if surgery is unsuccessful, severe asphyxia results in the death of the neonate, on average two days after birth. [11] The longest survival ever reported was six years. [27]

See also

Children's Hospital of Illinois Transplant surgery on Hannah Warren

Related Research Articles

<span class="mw-page-title-main">Trachea</span> Cartilaginous tube that connects the pharynx and larynx to the lungs

The trachea, also known as the windpipe, is a cartilaginous tube that connects the larynx to the bronchi of the lungs, allowing the passage of air, and so is present in almost all animals lungs. The trachea extends from the larynx and branches into the two primary bronchi. At the top of the trachea, the cricoid cartilage attaches it to the larynx. The trachea is formed by a number of horseshoe-shaped rings, joined together vertically by overlying ligaments, and by the trachealis muscle at their ends. The epiglottis closes the opening to the larynx during swallowing.

<span class="mw-page-title-main">Esophageal atresia</span> Congenital discontinuity of the oesophagus

Esophageal atresia is a congenital medical condition that affects the alimentary tract. It causes the esophagus to end in a blind-ended pouch rather than connecting normally to the stomach. It comprises a variety of congenital anatomic defects that are caused by an abnormal embryological development of the esophagus. It is characterized anatomically by a congenital obstruction of the esophagus with interruption of the continuity of the esophageal wall.

Tracheomalacia is a condition or incident where the cartilage that keeps the airway (trachea) open is soft such that the trachea partly collapses especially during increased airflow. This condition is most commonly seen in infants and young children. The usual symptom is stridor when a person breathes out. This is usually known as a collapsed windpipe.

<span class="mw-page-title-main">Respiratory tract</span> Organs involved in transmission of air to and from the point where gases diffuse into tissue

The respiratory tract is the subdivision of the respiratory system involved with the process of conducting air to the alveoli for the purposes of gas exchange in mammals. The respiratory tract is lined with respiratory epithelium as respiratory mucosa.

<span class="mw-page-title-main">Bronchus</span> Airway in the respiratory tract

A bronchus is a passage or airway in the lower respiratory tract that conducts air into the lungs. The first or primary bronchi to branch from the trachea at the carina are the right main bronchus and the left main bronchus. These are the widest bronchi, and enter the right lung, and the left lung at each hilum. The main bronchi branch into narrower secondary bronchi or lobar bronchi, and these branch into narrower tertiary bronchi or segmental bronchi. Further divisions of the segmental bronchi are known as 4th order, 5th order, and 6th order segmental bronchi, or grouped together as subsegmental bronchi. The bronchi, when too narrow to be supported by cartilage, are known as bronchioles. No gas exchange takes place in the bronchi.

<span class="mw-page-title-main">Tracheoesophageal fistula</span> Medical condition

A tracheoesophageal fistula is an abnormal connection (fistula) between the esophagus and the trachea. TEF is a common congenital abnormality, but when occurring late in life is usually the sequela of surgical procedures such as a laryngectomy.

Atresia is a condition in which an orifice or passage in the body is closed or absent.

<span class="mw-page-title-main">VACTERL association</span> Medical condition

The VACTERL association refers to a recognized group of birth defects which tend to co-occur. This pattern is a recognized association, as opposed to a syndrome, because there is no known pathogenetic cause to explain the grouped incidence.

<span class="mw-page-title-main">Lung bud</span> Embryological precursor of the respiratory system

The lung bud sometimes referred to as the respiratory bud forms from the respiratory diverticulum, an embryological endodermal structure that develops into the respiratory tract organs such as the larynx, trachea, bronchi and lungs. It arises from part of the laryngotracheal tube.

<span class="mw-page-title-main">Laryngotracheal stenosis</span> Medical condition

Laryngotracheal stenosis refers to abnormal narrowing of the central air passageways. This can occur at the level of the larynx, trachea, carina or main bronchi. In a small number of patients narrowing may be present in more than one anatomical location.

<span class="mw-page-title-main">Laryngotracheal groove</span>

The laryngotracheal groove is a precursor for the larynx and trachea.

The tracheoesophageal septum is an embryological structure. It is formed from the tracheoesophageal folds or ridges which fuse in the midline. It divides the oesophagus from the trachea during prenatal development. Developmental abnormalities can lead to a tracheoesophageal fistula.

<span class="mw-page-title-main">Bronchomalacia</span> Medical condition

Bronchomalacia is a term for weak cartilage in the walls of the bronchial tubes, often occurring in children under a day. Bronchomalacia means 'floppiness' of some part of the bronchi. Patients present with noisy breathing and/or wheezing. There is collapse of a main stem bronchus on exhalation. If the trachea is also involved the term tracheobronchomalacia (TBM) is used. If only the upper airway the trachea is involved it is called tracheomalacia (TM). There are two types of bronchomalacia. Primary bronchomalacia is due to a deficiency in the cartilaginous rings. Secondary bronchomalacia may occur by extrinsic compression from an enlarged vessel, a vascular ring or a bronchogenic cyst. Though uncommon, idiopathic tracheobronchomalacia has been described in older adults.

<span class="mw-page-title-main">Tracheobronchial injury</span> Damage to the tracheobronchial tree

Tracheobronchial injury is damage to the tracheobronchial tree. It can result from blunt or penetrating trauma to the neck or chest, inhalation of harmful fumes or smoke, or aspiration of liquids or objects.

Double aortic arch is a relatively rare congenital cardiovascular malformation. DAA is an anomaly of the aortic arch in which two aortic arches form a complete vascular ring that can compress the trachea and/or esophagus. Most commonly there is a larger (dominant) right arch behind and a smaller (hypoplastic) left aortic arch in front of the trachea/esophagus. The two arches join to form the descending aorta which is usually on the left side. In some cases the end of the smaller left aortic arch closes and the vascular tissue becomes a fibrous cord. Although in these cases a complete ring of two patent aortic arches is not present, the term ‘vascular ring’ is the accepted generic term even in these anomalies.

A laryngeal cleft or laryngotracheoesophageal cleft is a rare congenital abnormality in the posterior laryngo-tracheal wall. It occurs in approximately 1 in 10,000 to 20,000 births. It means there is a communication between the oesophagus and the trachea, which allows food or fluid to pass into the airway.

<span class="mw-page-title-main">Tracheobronchomalacia</span> Medical condition

Tracheobronchomalacia (TBM) is a condition characterized by flaccidity of the tracheal support cartilage which leads to tracheal collapse. This condition can also affect the bronchi. There are two forms of this condition: primary TBM and secondary TBM. Primary TBM is congenital and starts as early as birth. It is mainly linked to genetic causes. Secondary TBM is acquired and starts in adulthood. It is mainly developed after an accident or chronic inflammation.

<span class="mw-page-title-main">Tracheal deviation</span> Clinical sign

Tracheal deviation is a clinical sign that results from unequal intrathoracic pressure within the chest cavity. It is most commonly associated with traumatic pneumothorax, but can be caused by a number of both acute and chronic health issues, such as pneumonectomy, atelectasis, pleural effusion, fibrothorax, or some cancers and certain lymphomas associated with the mediastinal lymph nodes.

<span class="mw-page-title-main">Pulmonary agenesis</span> Medical condition

Pulmonary agenesis is an inborn lung underdevelopment that is rare and potentially lethal. The disorder is caused by a complete developmental arrest of the primitive lung during embryonic life, and it is often associated with other developmental defects. Bilateral and unilateral pulmonary agenesis are classified, depending on whether one side of the lung or both sides are affected. Bilateral pulmonary agenesis is lethal, while the mortality rate of unilateral pulmonary agenesis is higher than 50%. Depending on the severity, the symptom ranges from none to various respiratory complaints. It is detectable prenatally, however, its nonspecific clinical features act as the obstacle for diagnosing. The exact cause of pulmonary agenesis is still obscure. However, theories have been raised regarding the vascular, iatrogenic, viral and genetic causes of pulmonary agenesis in an attempt to explain the pathogenesis of the disorder. In most cases of pulmonary agenesis, surgical resection is performed to remove the malformed lobe or the entire defected lung of the patient depending on the severity of the respiratory impairment.

<span class="mw-page-title-main">Mandibulofacial dysostosis-microcephaly syndrome</span> Medical condition

Mandibulofacial dysostosis with microcephaly syndrome, also known as growth delay-intellectual disability-mandibulofacial dysostosis-microcephaly-cleft palate syndrome, mandibulofacial dysostosis, guion-almeida type, or simply as MFDM syndrome is a rare genetic disorder which is characterized by developmental delays, intellectual disabilities, and craniofacial dysmorphisms.

References

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