Tracheal agenesis (ORPHA:3346)
A rare congenital malformation characterized by either completely absent (agenesis), or severely underdeveloped (atresia) trachea. In both cases, the tracheal lumen is absent for at least a portion of its length, with no proximal-distal communication between the larynx and lower airways. Functionally and in terms of management, tracheal agenesis and tracheal atresia are equivalent.
Epidemiology
The prevalence at birth is less than 1 in 50 000. There is a male predominance (2:1 male-to-female ratio).
Clinical description
Associated congenital malformations are present in 90% of cases, most frequently affecting the cardiovascular or gastro-intestinal systems and the genito-urinary tract. Prenatal imaging may show signs of CHAOS (congenital high airway obstruction syndrome), including enlarged lungs, flattened or inverted diaphragm, fetal hydrops, and ascites. Polyhydramnios may be present. Tracheoesophageal fistula may also be present and cause decompression of the fetal lungs, which may obscure prenatal imaging signs of airway obstruction or CHAOS. Postnatal signs include aphonia, respiratory effort without air movement on auscultation, and inability to place an endotracheal tube. In patients with tracheoesophageal fistula, esophageal intubation may allow temporary oxygenation. Severity of agenesis may be described using the Floyd classification (type I: proximal tracheal agenesis with distal tracheoesophageal fistula; type II: absent trachea with carina arising from esophagus and leading to bronchi; type III: absent trachea and carina with bilateral mainstem bronchi arising directly from esophagus).
Etiology
No clear genetic cause or environmental contributors have been identified.
Diagnostic methods
Postnatally, the condition should be suspected in neonates presenting with polyhydramnios, respiratory distress, cyanosis and no audible cry, and in those in whom tracheal intubation proves impossible due to anatomic airway obstruction at or below the glottis. The diagnosis of TA is confirmed by direct laryngoscopy and a helical computerized tomography (CT) scan of the airway. A failure to perform esophageal intubation or an esophagoscopy may confirm presence of tracheoesophageal fistula; in some cases, a flexible bronchoscope may be passed via the esophagus and fistula into the lower airways.
Differential diagnosis
The differential diagnosis includes laryngeal atresia, severe glottic web (e.g with 22q11.2 microdeletion syndrome), congenital tracheal stenosis and VATER/VACTERL syndrome.
Antenatal diagnosis
Tracheal agenesis should be suspected in any fetus with prenatal imaging suggestive of CHAOS, particularly if the proximal airway fluid column on MRI extends into the larynx or proximal trachea. If tracheoesophageal fistula is present, there may be no clear signs of tracheal agenesis on prenatal imaging.
Management and treatment
If prenatal diagnosis is possible, careful counseling of the parents about the prognosis and typical clinical course is essential. Planned ex utero intrapartum treatment (EXIT) procedure may allow placement of a low or mediastinal tracheostomy if adequate distal trachea is present on prenatal imaging. If a concurrent tracheoesophageal fistula is present, oxygenation and ventilation may be achieved temporarily via esophageal intubation. Reconstruction may use the esophagus as a neotrachea, with or without external splinting or endoluminal stenting; subsequent alimentary tract reconstruction may use gastric pull-up or bowel interposition. Cadaveric tracheal allografts, 3D-printed grafts, and autologous free tissue reconstruction may provide other tracheal reconstructive options once the trachealized esophagus allows somatic growth.
Prognosis
This malformation is usually fatal in newborns; however, very rare cases of survival of several years have been reported with use of the esophagus in tracheal reconstruction.

                            Last update: 
                            August 2023


                            - Expert reviewer(s): 
                            Dr Karthik BALAKRISHNAN