The exact causes of<unk>  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. 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. Both organs regulate each other’s growth via molecular interactions. In<unk> , 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. The failure of the lung buds to develop from the primitive foregut leads to tracheoesophageal malformations. 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<unk> . Different degrees of this malformation result in different types of<unk> . Genetic determinants No clear genetic pattern or karyotype has been established to support the development of<unk> . 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. It is highly likely that<unk>  results from the mutation of several of these genes. 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. The Bmp family restricts the site of formation of lung buds as well as to induce cell proliferation via the suppression of Sox2. Gli2 and Gli3 null mutations were also found to result in delayed lung, tracheal and oesophageal development. 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. 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.
Tracheal agenesis
Persistent thyroglossal duct
Pulmonary hypoplasia
Pulmonary agenesis
Asphyxiating thoracic dysplasia
Laryngotracheal stenosis
Congenital diaphragmatic hernia
Pulmonary atresia