Congenital Aerodigestive Tract Anomalies

Congenital Aerodigestive Tract Anomalies

Christopher T. Wootten

Charles M. Myer III


The aerodigestive tract includes an array of organs and tissues with specialized roles that begins at the nares and lips proximally and ends at the stomach and bronchioles distally. Despite the disparate anatomy, these organs and tissues are united around three common functions: feeding, breathing, and voicing. Disease at any level of the aerodigestive tract often affects all three functions. Congenital malformations of the upper aerodigestive tract usually relate to errors in the embryonic phase of development. Dividing anomalies by anatomical region provides organizational structure to the differential diagnosis and aids in the formulation of a focused and cost-effective diagnostic algorithm. A comprehensive list of congenital aerodigestive tract diseases by anatomical location is given in Table 87.1. Aerodigestive embryology is reviewed below.

Nasal and Nasopharyngeal

The stomodeum is surrounded by the frontonasal prominence superiorly, the maxillary processes laterally, and the mandibular processes inferiorly. Normal nasal development occurs during weeks 4 through 12 of intrauterine life. Within this timeframe, the foramen cecum provides communication between the prenasal space and the anterior neuropore. The nasal placodes, which are two small thickenings in the frontonasal prominence, burrow to form nasal pits (Fig. 87.1). This invagination process in the fifth week creates ridges of tissue around the pits called the lateral nasal prominences laterally and the medial nasal prominences medially. The nasolacrimal ducts develop as ectodermal thickenings that become buried in the mesoderm of the nasal pits between the lateral nasal prominence and the maxillary process. This buried ectoderm eventually canalizes from superiorly to inferiorly. The lateral nasal prominences form the nasal alae. Posteriorly, the nasal pits develop into the pouches of the nose and paranasal sinuses that reside above the oral and buccal cavities. The nasobuccal membrane separates the nasal and oral-buccal spaces, and eventually this membrane ruptures and obliterates (1). Several gene products have been identified that play regulatory roles in posterior nasal development, including PTPN14 (2), TBX22 (3), and CHD7 (mutated in greater than 50% of patients with CHARGE syndrome) (4).


As early as the third week, the branchial arches are demonstrated surrounding the foregut and primitive oral cavity, or stomodeum. The stomodeum is separated from the developing nose by the nasobuccal membrane and from the developing foregut by the buccopharyngeal membrane, the latter corresponding to the region of the palatine tonsils. The mandibular arch begins to grow anteriorly around the third week, enlarging the stomodeum. The mandibular arch subdivides into a maxillary and mandibular process, and the paired maxillary and mandibular processes from each side eventually fuse in the midline along neural crest cell migrations (5). Recalling nasal development, the lateral and medial prominences finalize interaction with the developing maxillary process, creating the philtrum and medial lip (from the fused medial nasal prominences) and the lateral upper lip (from the maxillary prominences). As palatal development occurs, the deepening nasal pits become separated from the developing oral cavity and tongue. Oral-nasal patterning of the palate as well as some aspects of oral cavity and tongue development (e.g., the development of taste buds) is under sonic hedgehog (Shh) regulation (6,7,8,9,10). Palatal development
is complex, and the numerous steps involved are detailed elsewhere in this text.







Pyriform aperture stenosis

Median mandibular cleft

Vallecular cyst

Branchial fistula


Facial clefts


Lingual thyroid



Nasolacrimal duct cysts

Cleft lip

Lingual thyroglossal duct cyst

Pharyngeal bands

Complete tracheal rings


Cleft palate

Teratoma Hemangioma



Midpalatal cyst of infancy

Maxillary duplication

Vascular malformation

Deficient tracheal rings


Nasolabial cyst

Persistent buccopharyngeal membrane

Cricopharyngeal bar



Nasopalatine duct cyst



Tracheal agenesis


Labial frenulum


Vocal cord paralysis

Bronchogenic cyst

Choanal atresia

Oral synechia


Subglottic stenosis

Tracheal bronchus

Thornwaldt cyst

Lip pits


Posterior glottic stenosis

Laryngotracheal stenosis



Desmoid fibromatosis

Laryngotracheal cleft

Epidermolysis bullosa

Salivary gland anlage tumor


Branchial fistula

Bifid epiglottis

Tracheal pouch/tracheocele


Congenital macrostomia

Pharyngeal bands

Epiglottic cyst




Ectopic parotid tissue

Laryngeal saccular cyst

Vascular malformation

Ossifying fibroma

Median rhomboid glossitis

Ectopic carotid



Pyogenic granuloma

Fissured tongue

Vascular malformation



Infantile myofibromatosis



Epiglottic agenesis

Esophageal duplication cyst


Lingual thyroid

Pharyngeal auricle

Epiglottic hypoplasia

Esophageal stricture


Lingual thyroglossal duct cyst


Laryngeal web

Dysphagia lusoria



Laryngeal atresia

Broncho-biliary fistula



Submucous laryngeal cleft

Tracheal web


Epidermoid cyst


Pleomorphic adenoma

Dermoid cyst

Subglottic hemangioma


Lymphoepithelial cyst


Soft tissue sarcomas


Sulcus vocalis

Birth trauma


Laryngeal cyst

Bohn nodule

Pachyonychia congenita

Natal teeth

Ectopic thymic cyst



Lymphatic malformation


Proteus syndrome


Posteriorly, the tongue develops from multiple branchial arch contributions. Around the fourth week, four regions fuse to form the tongue: paired lateral lingual swellings (first arch derivatives), a midline lingual swelling (first arch derivative), and a hypobranchial eminence (second, third, and fourth arch derivatives). The first arch-derived tongue lies anterior to the buccopharyngeal membrane and constitutes the oral tongue that represents the anterior two-thirds of the tongue’s length. In contrast, the portion of the tongue derived from the hypobranchial eminence becomes the oropharyngeal, or posterior onethird of the tongue. As the four zones of the tongue fuse, the lateral lingual swellings override the midline lingual swelling, which comes to be known as the tuberculum impar. Immediately posterior to the tuberculum impar is a V-shaped sulcus (the sulcus terminalis) that separates the tuberculum impar from the hypobranchial eminence, now known as the copula. In the midline of the sulcus terminalis is a zone known as the foramen cecum, which is the origin of the mesodermally derived thyroid gland (Fig. 87.2) (5).

Figure 87.1 Lateral and frontal drawing of a human embryo around 5 weeks. 1, lateral nasal prominence; 2, medial nasal prominence; 3, maxillary process; 4, mandibular process; 5, stomodeum. Adapted from Nelson, 1953.

Hypopharyngeal and Laryngeal

Posterior to the hypobranchial eminence (inferior in postnatal life), the larynx appears as a thickening along the ventral aspect of the foregut around 28 days. The caudal portion of the hypobranchial eminence (also known as the furcula of His) gives rise to an epiglottic anlage by 33 days. Paired fourth branchial arches contribute to the epiglottis and the aryepiglottic folds, but the hypobranchial eminence may also have unpaired midline derivatives. By 48 days, the vallecular space is well-defined enough to distinguish the epiglottis from the tongue (11). Inferiorly, the respiratory primordium develops an outpouching from the floor of the pharynx that begins to proliferate posteriorly. This laryngotracheal complex becomes continuous with the ventral lung buds. Obliteration of the ventral lumen of the primitive laryngopharynx gives rise to the epithelial lamina of the larynx. The pharyngoglottic duct is located dorsal to the epithelial lamina, and the laryngeal cecum (primitive vestibule) is located anterior to it. The epithelial lamina recanalizes to open into the laryngeal cecum and allows the pharyngoglottic duct to unite with the cecum, forming the vestibule (from the cecum) and the interarytenoid notch/posterior glottis (from the pharyngoglottic duct) (12). Beneath these epithelial movements, mesenchymal contributions from the paired fourth and sixth branchial arches comprise the cartilaginous framework of the larynx and its supporting nerves and vessels.

Figure 87.2 Posterior coronal illustration depicting the developmental anatomy of the tongue around the fifth week of development. 1, lateral lingual swelling; 2, tuberculum impar; 3, sulcus terminalis; 4, hypobranchial eminence (copula); 5, epiglottic anlage; 6, glottic inlet.

Tracheobronchial and Esophageal

Again, around 28 days, the anterior foregut begins to partition into a dorsal esophagus and a ventral trachea that connects to simultaneously developing ventral lung buds off the primitive foregut. The molecular mechanisms driving this early partition include the localized expression of Nkx2-1 (Tif1) in the ventral wall of the anterior foregut, while Sox2 expression predominates dorsally. Patterning of Nkx2-1/Sox2 expression is in turn signaled by the expression of Bmps, noggin, Fgfs, Shh, and Wnts in the surrounding mesenchyme. Abnormalities in these mesenchymal signals can result in failure of foregut separation and abnormal differentiation of the epithelium and mesenchyme, including tracheal agenesis (13). Tracheoesophageal separation is a dynamic process that involves inward movement of lateral mesodermal ridges. This infolding proceeds in a posterior to anterior (inferior to superior, postnatally) direction according to the classic model of tracheoesophageal embryogenesis. Alternative theories depict a series of cranial and caudal folds along the evolving tracheoesophageal septum, and epithelial proliferation and apoptosis may play a role in the division of the trachea and esophagus as well (14). As the trachea is separating from the esophagus, the tracheal mesoderm is differentiating into C-shaped cartilage rings anterolaterally. Contrasting mesenchymal development occurs along the newly formed posterior tracheal wall where strips of smooth muscle are formed. The development of smooth muscle posteriorly and cartilage anteriorly at regular intervals is guided by differential expression of Fgf10 and Shh (15). Likewise, Fgf10 plays an essential role alongside Fgfr2 in the branching morphogenesis of the lung buds (13). By the end of intrauterine life, the trachea averages 5.7 cm in length, having 18 to 20 cartilaginous rings. Mesenchymal differentiation
within the esophagus results in a muscular layer of striated muscle in the upper one-third and smooth muscle in the lower two-thirds of the tube (16).