Congenital anomalies of the larynx

INTRODUCTION — 

Congenital anomalies are the product of errors in embryogenesis (malformations) or the result of intrauterine events that affect embryonic and fetal growth (deformations and disruptions) [1]. The more complex the formation of a structure, the more opportunities for malformation.

Disruptions and defects in the formation and growth of the larynx can lead to a variety of malformations which generally present with stridor and breathing difficulties in early infancy (table 1).

This topic provides an overview of some of the most common congenital anomalies of the larynx. Related topics include:

●(See "Assessment of stridor in children".)

●(See "Common causes of hoarseness in children".)

●(See "Congenital laryngomalacia".)

●(See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula".)

EMBRYOLOGY — 

The formation of a median pharyngeal groove presages the appearance of the respiratory tract. At approximately 25 days of intrauterine life, the anlagen of the larynx, trachea, bronchi, and lungs arise from a ventromedial diverticulum of the foregut called the tracheobronchial groove. The cartilage of the trachea and connective tissue and muscle of the trachea and esophagus are derived from splanchnic mesenchyme. Lateral furrows develop on each side of the ventromedial diverticulum, deepen, and join to form the tracheoesophageal septum [2-4].

The distal esophagus can be distinguished from the stomach and the laryngeal primordia appear at approximately 33 days of intrauterine life. The T-shaped laryngeal slit (aditus) is formed anteriorly by the growth of the primordium of the epiglottis (from the hypobranchial eminence, arches III and IV) and laterally by the precursors of the arytenoid cartilages (ventral ends of arch VI) [2-4].

During the fifth and sixth weeks, the tracheoesophageal septum extends to the first tracheal ring. By the time the embryo is 13 to 17 mm in length, laryngeal cartilage and muscle development are clearly identifiable and lateral cricoid condensation is underway. By the seventh week of development, the cricoid ring is complete and the cartilaginous hyoid is visible below the epiglottis (picture 1). Definitive tracheal cartilage appears at this stage, and the esophagus has four discrete layers. The larynx, trachea, and esophagus are well formed by the end of the embryologic period (image 1) [2-4].

LARYNGOMALACIA — 

Congenital laryngomalacia is one of the most common causes of noisy breathing in infancy. Affected patients usually present with inspiratory stridor that begins in the newborn period and peaks at four to eight months of age. The diagnosis is made with awake flexible fiberoptic laryngoscopy (FFL) demonstrating an omega-shaped epiglottis, short aryepiglottic folds, and collapse of the supra-arytenoid tissue into the glottic inlet during inspiration (movie 1 and picture 2). A retro-displaced epiglottis may also be present (movie 2), especially in children with underlying neurologic disorders.

In children who are otherwise healthy, laryngomalacia typically resolves over time as the child grows. Most patients outgrow stridor by 24 months of age. By contrast, laryngomalacia tends to persist in children who have underlying neuromuscular disorders and genetic syndromes. Severely affected patients often require surgery (supraglottoplasty) (picture 3 and movie 3).

The evaluation and management of congenital laryngomalacia is discussed in greater detail separately. (See "Congenital laryngomalacia".)

Congenital laryngomalacia is distinct from tracheomalacia (an abnormally compliant trachea), which is far less common. Laryngomalacia causes inspiratory stridor, whereas tracheomalacia causes expiratory or biphasic stridor. In addition, tracheomalacia is often associated with other congenital malformations such as tracheoesophageal fistula or vascular rings. Tracheomalacia is discussed in greater detail separately. (See "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Tracheomalacia'.)

CYSTS

Vallecular cysts — Congenital vallecular cysts contain respiratory epithelium and mucous glands. They arise in the hypopharynx between the epiglottis and base of tongue (picture 4 and picture 5). Vallecular cysts are an uncommon cause of respiratory distress in infancy [5,6]. Infants with vallecular cysts typically present with feeding difficulty, failure to thrive, stridor, noisy breathing, respiratory distress, or a hoarse cry. Diagnosis is confirmed with FFL. There may be associated laryngomalacia seen on FFL in some cases [5-8]. Preoperative computed tomography (CT) or magnetic resonance imaging (MRI) can demonstrate the relationship of the lesion to surrounding structures [9].

Definitive treatment requires marsupialization, which can be performed transorally with microscissors or laser, or through a transhyoid resection [5,10-12]. Aspiration or rupture may provide temporary improvement in symptoms but seldom provides permanent treatment.

Laryngoceles and saccular cysts — Congenital laryngoceles and saccular cysts are abnormal dilations of the laryngeal saccule and arise in the region of the laryngeal ventricle. Laryngoceles are outpouchings of the saccular mucosa. They may remain within the confines of the cartilaginous larynx (internal laryngoceles) or extend through the thyrohyoid membrane to present as neck masses (combined laryngoceles). Saccular cysts are fluid-filled submucosal cysts that are covered by a normal mucous membrane and isolated from the interior of the larynx [13].

These anomalies typically are asymptomatic; however, they may cause upper airway obstruction (particularly in the neonate), hoarseness, dysphagia, dyspnea, and laryngeal discomfort [14-17]. The symptoms caused by laryngoceles are episodic because laryngoceles intermittently fill with air. In contrast, the symptoms produced by saccular cysts are more constant [17].

Laryngoceles and saccular cysts usually are discovered incidentally during radiologic evaluation for unrelated symptoms. Laryngoceles are visualized as fluid- and air-containing cystic masses on plain radiography, ultrasound, or CT [16]. CT is preferred for determination of the full extent of the lesion and its relation to the larynx (image 2).

If surgical resection is necessary, complete resection may be more effective than marsupialization. In one large series, complete resection of the saccular cyst wall using a carbon dioxide (CO₂) laser and microsuturing was associated with lower recurrence rates compared with marsupialization [18].

LARYNGEAL ATRESIA — 

Laryngeal atresia is thought to be caused by the failure of epithelial growth and recanalization in the vestibule and subglottic regions [19].

Most infants with laryngeal atresia present with asphyxia at the time of birth. Performing an emergency tracheotomy soon after delivery is necessary for survival because the imperforate larynx cannot be intubated [20]. Laryngeal atresia can be identified by antenatal ultrasonography in fetuses presenting with congenital high airway obstruction syndrome [21]. An ex utero intrapartum treatment (EXIT) procedure with tracheotomy is potentially lifesaving [22]. However, fetuses with laryngeal atresia often have other severe congenital malformations that may be fatal (eg, lung hypoplasia, tracheal agenesis, hypoplastic left heart syndrome, bilateral renal agenesis, esophageal atresia) [23].

LARYNGEAL WEBS — 

Laryngeal webs are rare congenital anomalies caused by failure of resorption of the epithelial layer that obliterates the laryngeal opening in normal development. This results in incomplete separation of the vocal folds (picture 6 and picture 7). Webs can occur anywhere along the anterior or posterior larynx. Laryngeal webs also can result from trauma to the airway (eg, from intubation, traumatic injury, or prior surgical manipulation). (See "Common causes of hoarseness in children", section on 'Trauma'.)

Laryngeal webs are categorized according to size [24]:

●Type 1 – Involving <35 percent of the glottis; they are typically thin or membranous

●Type 2 – Involving 35 to 50 percent of the glottis (figure 1)

●Type 3 – Involving 50 to 75 percent of the glottis, often extending to the anterior cricoid cartilage (picture 7)

●Type 4 – Involving up to 99 percent of the glottis

Approximately 10 percent of patients with laryngeal webs have other associated anomalies, principally of the upper respiratory tract (eg, subglottic stenosis, submucous cleft palate) [25,26]. In addition, laryngeal webs are associated with cardiac defects (particularly, ventricular septal defects [27,28]) and may occur in conjunction with 22q11 deletion as part of the DiGeorge/velocardiofacial syndrome. (See "DiGeorge (22q11.2 deletion) syndrome: Epidemiology and pathogenesis" and "Syndromes with craniofacial abnormalities", section on 'Velocardiofacial (Shprintzen) syndrome'.)

Patients with laryngeal webs usually present in infancy with respiratory distress and a weak or high-pitched cry [25,29]. Symptoms in those who present later in life include hoarse or weak voice, breathiness, and varying degrees of dyspnea and stridor depending upon the degree of airway compromise. (See "Assessment of stridor in children".)

Treatment of laryngeal webs depends upon the degree of airway obstruction. Simple anterior commissure webs are treated surgically, either by lysis of the web with a carbon dioxide (CO₂) laser or sharp division with a knife. Laryngeal reconstruction with or without a laryngeal stent may be indicated in patients with webs that involve larger portions of the anterior and posterior glottis [30]. Recurrent webbing is common following attempts at either endoscopic or open repair [24].

CONGENITAL SUBGLOTTIC STENOSIS — 

Congenital subglottic stenosis is a narrowing of the lumen of the cricoid region, possibly caused by incomplete canalization of the cricoid ring (diameter less than 4 mm in the term infant and 3 mm in the preterm infant) [19,31]. It presents most commonly as recurrent croup but if severe, it may cause biphasic stridor in a newborn. Familial congenital subglottic stenosis has been described [32].

Congenital subglottic stenosis is differentiated from acquired subglottic stenosis by the absence of history of trauma or instrumentation and by less severe symptoms. (See "Complications and long-term pulmonary outcomes of bronchopulmonary dysplasia", section on 'Glottic and subglottic damage'.)

Congenital subglottic stenosis typically improves as the larynx grows. Fewer than one-half of affected children require tracheostomy. Depending upon the severity of the obstruction and the need for supplemental oxygen therapy, congenital subglottic stenosis also may be treated by endoscopic division of cartilage with balloon dilation, anterior-cricoid split with posterior cartilage graft, or partial cricotracheal resection [19,33-36].

LARYNGEAL CLEFTS — 

Posterior laryngeal clefts are thought to result from failed fusion of the two lateral growth centers of the posterior-cricoid cartilage at six to seven weeks of intrauterine life. The smallest clefts may involve only the interarytenoid region, whereas more extensive aborted development of the tracheoesophageal septum can result in a large laryngotracheoesophageal cleft that extends to the carina [37,38].

Laryngeal clefts occur in approximately 1 in 10,000 to 1 in 20,000 live births [39]. They are more common in boys than girls, with a male:female ratio of 5:3 [40,41]. Clefts of the larynx and trachea/esophagus can occur in isolation, or as part of a syndrome (eg, Opitz-Frias, VATER/VACTERL, Pallister-Hall, CHARGE), or with other associated malformations (gastrointestinal, genitourinary, cardiac, craniofacial) [42].

Children with posterior laryngeal clefts may present with increased secretions, feeding difficulty, failure to thrive, wheezing, stridor, noisy breathing, aspiration, respiratory distress, recurrent pulmonary infections, and/or hoarseness [19,43,44]. In one series of 41 children with type 1 posterior laryngeal clefts, the average age at onset of symptoms was five months and the average age at diagnosis was three years [43]. Children with posterior laryngeal clefts often have associated gastroesophageal reflux (GER), tracheomalacia, developmental delay, and/or additional congenital anomalies [19,43-45].

The diagnosis is based upon a high index of suspicion and is supported by modified barium swallow that shows leakage of barium into the airway [19,44]. Leakage occurs at the laryngeal introitus, rather than the distal trachea as is seen in H-type fistulae. Rigid endoscopy is the standard for diagnosis and should include endoscopic palpation of the interarytenoid area (picture 8) [43,46].

Posterior laryngeal clefts and laryngotracheoesophageal clefts may be classified according to anatomic or clinical criteria. The Benjamin classification describes five types (figure 1) [47]:

●Occult clefts can be appreciated only by palpation and measurement of the interarytenoid height

●Type 1 clefts are limited to the supraglottic, interarytenoid area (picture 8)

●Type 2 clefts show partial clefting of the posterior cricoid cartilage, sometimes with a mucosal bridge across the cartilaginous gap

●Type 3 clefts involve the entire cricoid and the cervical portion of the tracheoesophageal membrane, stopping above the thoracic inlet

●Type 4 clefts involve a major portion of the intrathoracic tracheoesophageal wall (picture 9)

The treatment for laryngotracheoesophageal clefts depends upon the type of cleft and severity of associated symptoms. Minor clefts (type 1 and occult clefts) sometimes can be managed without surgery if medical therapy can control GER and aspiration [19,43]. Injection of the interarytenoid region with fillers, such as hyaluronic acid, can help decrease aspiration temporarily as the child grows [48-50]. Local endoscopic procedures can also be attempted on smaller-sized clefts. Operative repair of extensive clefts typically requires collaboration of the otolaryngologist and thoracic surgeon [51]. A series of transoral robotic repair of small clefts have been reported with results similar to endoscopic repair [52]. (See "Gastroesophageal reflux disease in children and adolescents: Management".)

SUBGLOTTIC HEMANGIOMAS — 

Infantile hemangiomas are congenital vascular tumors that characteristically undergo a rapid growth phase during the first several months after birth, followed by a spontaneous involution phase. They may present as solitary lesions or as part of a segmental hemangioma syndrome. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications", section on 'Localized lesions' and "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications", section on 'Segmental lesions'.)

Infantile hemangiomas are two to three times more common among females than males. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications", section on 'Epidemiology and risk factors'.)

The likelihood of developing a subglottic hemangioma is greatest in infants with cutaneous hemangiomas located in a cervicofacial, mandibular, or "beard" distribution (picture 10). In these patients, the development of progressive hoarseness or stridor strongly suggests a subglottic hemangioma. However, isolated subglottic hemangiomas can develop in infants who do not have cutaneous hemangiomas.

The presentation may be similar to that of subglottic stenosis, with recurrent croup and biphasic stridor.

The diagnosis is confirmed with rigid airway endoscopy, which typically reveals a red to blue, compressible, sessile lesion that is most commonly located in the posterolateral subglottis (picture 11 and picture 12). Plain radiographs of the neck typically demonstrate asymmetric narrowing of the subglottis. CT with contrast may be useful in delineating large hemangiomas or those extending beyond the confines of the larynx.

Propranolol is the first-line therapy for subglottic hemangiomas, but surgery retains a role in the management of extensive or recurrent lesions [53]. Medical treatment is discussed separately. (See "Infantile hemangiomas: Management", section on 'First-line therapy'.)

SUMMARY AND RECOMMENDATIONS

●Laryngomalacia – Congenital laryngomalacia is one of the most common causes of recurrent or chronic noisy breathing in infancy. Affected patients usually present with inspiratory stridor that begins in the newborn period and peaks at four to eight months of age. The diagnosis is made with awake flexible fiberoptic laryngoscopy demonstrating an omega-shaped epiglottis, short aryepiglottic folds, and collapse of the supra-arytenoid tissue into the glottic inlet during inspiration (movie 1 and picture 2). This disorder is discussed in greater detail separately. (See "Congenital laryngomalacia".)

●Vallecular cysts – Infants with vallecular cysts (picture 4 and picture 5) typically present with feeding difficulty, failure to thrive, stridor, noisy breathing, respiratory distress, or a hoarse cry. Laryngomalacia is an associated finding. Diagnosis is confirmed with endoscopy of the hypopharynx. (See 'Vallecular cysts' above.)

●Laryngoceles and saccular cysts – Congenital laryngoceles and saccular cysts typically are asymptomatic; however, they may cause upper airway obstruction (particularly in the neonate), hoarseness, dysphagia, dyspnea, and laryngeal discomfort. The symptoms caused by laryngoceles are episodic because laryngoceles intermittently fill with air. The symptoms produced by saccular cysts are constant. (See 'Laryngoceles and saccular cysts' above.)

●Laryngeal atresia – Most infants with laryngeal atresia present with asphyxia at the time of birth. Emergency tracheotomy is necessary for survival. (See 'Laryngeal atresia' above.)

●Laryngeal webs – Laryngeal webs are rare congenital anomalies caused by failure of resorption of the epithelial layer at the laryngeal opening, resulting in incomplete separation of the vocal folds (picture 6 and picture 7). Patients with laryngeal webs usually present in infancy with respiratory distress and an unusual cry. Approximately 10 percent of patients with laryngeal webs have other associated anomalies. Treatment is surgical and depends on the degree of airway obstruction. (See 'Laryngeal webs' above.)

●Subglottic stenosis – Congenital subglottic stenosis is a narrowing of the lumen of the cricoid region. It presents most commonly as recurrent croup but may cause biphasic stridor in a newborn if severe. It is differentiated from acquired subglottic stenosis by the absence of history of trauma or instrumentation and by less severe symptoms. Congenital subglottic stenosis typically improves as the larynx grows; however, surgical intervention may be necessary in some children. (See 'Congenital subglottic stenosis' above.)

●Laryngeal clefts – Children with posterior laryngeal clefts may present with increased secretions, feeding difficulty, failure to thrive, wheezing, stridor, noisy breathing, aspiration, respiratory distress, recurrent pulmonary infections, and/or hoarseness. Contrast studies of the esophagus may show spillage of barium into the airway. Rigid endoscopy is the standard for diagnosis and should include palpation of the interarytenoid area (picture 8 and picture 9). (See 'Laryngeal clefts' above.)

●Hemangiomas – Infantile hemangiomas are congenital vascular tumors that characteristically undergo a rapid growth phase during the first several months after birth. Subglottic hemangiomas can develop in infants who do not have cutaneous hemangiomas. However, the risk is greatest with segmental hemangiomas located in a cervicofacial, mandibular, or "beard" distribution (picture 10). The presentation may be similar to that of subglottic stenosis with recurrent croup and biphasic stridor. The diagnosis is confirmed endoscopically (picture 11 and picture 12). Propranolol is generally the first-line therapy for subglottic hemangiomas, as discussed separately. (See "Infantile hemangiomas: Management", section on 'First-line therapy'.)