Congenital anomalies of the jaw, mouth, oral cavity, and pharynx

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. (See "Congenital anomalies: Approach to evaluation".)

Defects in the formation and growth of the jaw, oral cavity, and pharynx lead to a variety of malformations. The embryology, clinical features, and management of congenital anomalies of the oral cavity and pharynx are reviewed here. Congenital anomalies of the ear, nose, and upper aerodigestive tract are discussed separately. (See appropriate topic reviews.)

EMBRYOLOGY — The oral cavity is separated from the nasal cavity posteriorly by midline fusion of the secondary palate and anteriorly by the approximation of the primary palate to these shelves [2]. The two one-halves of the lower jaw arise from mesenchyme derived from the first branchial arch (figure 1) and eventually fuse medially. Midline union of the mandibular portions of the first branchial arches, the earliest fusion event in the face, normally occurs during the fourth week of intrauterine life.

The anterior two-thirds of the tongue are formed from two lateral swellings that arise from the first branchial arch. The posterior one-third of the tongue develops behind the foramen cecum from second arch mesenchyme. Thus, the anterior and posterior sections of the tongue have separate innervations and blood supplies [3].

The parotid glands arise from solid epithelial cords that proliferate from the ectodermal lining of the primitive mouth. The submandibular glands are of endodermal origin [4].

JAW ANOMALIES — Failed mandibular fusion may result in mandibular clefting (picture 1) and hypoplasia of the mandible [5]. Retarded growth of the mandible causes micrognathia.

Micrognathia — Micrognathia in the older child primarily is a cosmetic problem. In contrast, micrognathia in the neonate may cause upper respiratory obstruction. In addition, micrognathia results in an oral cavity that is disproportionately small for the tongue (ie, glossoptosis or relative macroglossia).

Pierre Robin sequence — When present during the later weeks of embryogenesis, micrognathia with relative macroglossia (glossoptosis) can inhibit the ingrowth and fusion of the secondary palatal shelves. The triad of micrognathia, glossoptosis, and a U-shaped palatal cleft describes the Pierre Robin sequence (also known as Robin sequence or Pierre Robin syndrome) (picture 2A-B). (See "Syndromes with craniofacial abnormalities", section on 'Pierre Robin sequence'.)

Pierre Robin sequence often occurs as part of a syndrome, most commonly Stickler syndrome or 22q11.2 deletion syndrome (velocardiofacial syndrome), accounting for approximately 11 percent of patients with Pierre Robin sequence [6]. (See "Syndromes with craniofacial abnormalities", section on 'Stickler and Marshall syndromes' and "DiGeorge (22q11.2 deletion) syndrome: Clinical features and diagnosis".)

Children with the Pierre Robin sequence may have associated gastroesophageal reflux [7] and conductive hearing loss [8]. (See "Clinical manifestations and diagnosis of gastroesophageal reflux disease in children and adolescents" and "Hearing loss in children: Screening and evaluation".)

Infants with the Pierre Robin sequence may have upper airway obstruction in the neonatal period [9,10]. In most cases, prone positioning and gavage feeding are the only interventions necessary [11,12]. The use of a nasal trumpet also may be undertaken as part of conservative management (picture 2B).

In severe cases, surgical intervention may be required to correct life-threatening upper airway obstruction [13]. Surgical options include:

●Tracheostomy – This has traditionally been the intervention performed in this setting. The tracheostomy tube remains in place until the child has grown such that the airway is larger and no longer obstructed. As discussed below, mandibular distraction osteogenesis has become the preferred approach at many tertiary centers rather than primary tracheostomy. Nevertheless, tracheostomy remains an important surgical tool in this patient population, particularly at centers with less experience with mandibular distraction.

●Glossopexy – Glossopexy or tongue-lip adhesion has been advocated by some as a temporizing measure [14,15]. In this procedure, the tongue is sutured to the lower lip and gingiva to prevent tongue prolapse.

●Mandibular distraction osteogenesis – Mandibular distraction has largely supplanted lip-tongue adhesion and primary tracheotomy at most major centers [16,17]. It can be performed in the neonatal period in an effort to avoid a tracheotomy (picture 3) [18-20]. The procedure involves bilateral division of the mandibular body and gradual advancement (1 to 2 mm/day) with an adjustable fixation device. The choice of external (on the facial skin) or internal (in the mouth) distraction devices remains controversial (picture 3) [21]. New bone is gradually laid down in the bony defect over a six-week period. The tongue is progressively moved forward with the mandible, improving the airway. Complications of this technique include dental and sensory defects and, rarely, injury to the facial nerve [22].

Surgical closure of the palatal defect often is deferred in children with Pierre Robin sequence until the airway is stable [23]. Management of children with Pierre Robin sequence is discussed in greater detail separately. (See "Syndromes with craniofacial abnormalities", section on 'Management of Pierre Robin sequence'.)

Jaw fusion anomalies — Fusional anomalies joining the mandible to the maxilla are rare. They include both bony fusions and soft tissue adhesions [24]. The terms "congenital syngnathia," "congenital alveolar fusion," and "congenital oral synechia" are variably used to describe these defects. Associated anomalies (especially cleft palate) and syndromes (especially multiple pterygium syndrome and Van der Woude syndrome) are found in more than one-half of affected infants. These children present challenges in early feeding and nutrition. During planned surgical correction, airway management can be difficult and tracheostomies were performed in one-third of reported cases [24,25]. Long-term surgical results are favorable, but continuing physiotherapy is often needed to maintain jaw mobility [25].

LIP ANOMALIES

Clefting — Clefting anomalies of the upper lip are more common and more varied than clefting anomalies of the lower lip because fusion of the components of the upper lip occurs later in embryogenesis and is more complex than fusion of the lower lip. Cleft lip and palate are described separately. (See "Overview of craniofacial clefts and holoprosencephaly" and "Etiology, prenatal diagnosis, obstetric management, and recurrence of cleft lip and/or palate".)

Microstomia — Complete union of the upper and lower lips results in astomia. Microstomia refers to the rudimentary oral aperture that occasionally is seen in association with severe forms of holoprosencephaly [26]. Microstomia also may be seen in fetal valproate syndrome, trisomy 18, and Hallermann-Streiff syndrome [27].

Macrostomia — Macrostomia, also known as transverse facial cleft, occurs as part of the Angelman, Morquio, Noonan, Beckwith-Wiedemann, Treacher-Collins, and Williams syndromes [27,28]. Lateral clefting of the oral introitus causes asymmetric macrostomia. Surgical correction of macrostomia may require the creation of a new oral commissure (picture 4) [29]. (See "Congenital anomalies of the nose", section on 'Holoprosencephaly'.)

Lip pits — Congenital pits of the upper lip are extremely uncommon [30]. Congenital pits of the lower lip typically present as bilateral, paramedian depressions in the vermilion border [31]. They represent small accessory salivary glands that are thought to arise from secondary notching of the epithelium of the lip and often secrete mucous from the salivary glands at their bases. Rarely, lip pits may communicate with an ectopic parotid duct [32].

Lip pits are inherited in an autosomal dominant fashion in van der Woude syndrome (lower lip pits with or without cleft lip and/or palate, with or without missing second premolars) (picture 5). Mutations and polymorphisms of the IRF6 gene are common causes of van der Woude syndrome as well as nonsyndromic cleft lip/cleft palate [33]. Lip pits may also be part of other syndromes (eg, basal cell nevus syndrome, branchio-oto-renal syndrome, Kabuki syndrome). (See "Syndromes with craniofacial abnormalities", section on 'Van der Woude syndrome'.)

Labial frenula — Abnormalities of the labial frenula occur in both the upper and lower lips. In infancy, the maxillary (upper) labial frenulum typically extends over the alveolar ridge to form a raphe that reaches the palatal papilla [34]. Some believe that a tight upper lip tie can adversely affect breastfeeding in a manner similar to ankyloglossia (tongue-tie). However, there is little objective evidence to support the association of upper lip tie and breastfeeding difficulties [35]. The persistence of this raphe during dental eruption may lead to widely spaced central incisors (diastema). Similarly, the traction caused by the extension of the mandibular (lower) labial frenulum to the interdental papilla may cause periodontal disease and bone loss. (See "Ankyloglossia (tongue-tie) in infants and children", section on 'Upper lip tie'.)

TONGUE ANOMALIES — Congenital lesions of the tongue include cysts (picture 6) [36], mucoceles, macroglossia, ankyloglossia (picture 7), lingual thyroid, and median rhomboid glossitis.

Macroglossia — Macroglossia is a true enlargement of the tongue, in contrast with glossoptosis (relative macroglossia), in which a normally sized tongue fills a small oral cavity. Macroglossia can be focal or generalized.

●Focal enlargement of the tongue usually is caused by congenital tumors, particularly lymphatic malformations and hemangiomas (picture 8 and picture 9). It also may occur in patients with multiple endocrine neoplasia type 2B. When tongue enlargement is caused by lymphatic malformations, the surface of the tongue is pebbly, with multiple vesicle-like blebs (superficial dilated lymphatic channels) (picture 10) [28]. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications" and "Clinical manifestations and diagnosis of multiple endocrine neoplasia type 2".)

●Enlargement of one-half of the tongue can be seen in patients with somatic hemihypertrophy.

●Generalized macroglossia is seen in Beckwith-Wiedemann syndrome [37] and untreated hypothyroidism. Enlargement of the tongue in patients with Beckwith-Wiedemann syndrome or hypothyroidism is usually smooth, whereas a multinodular appearance is seen with other causes of macroglossia [28]. (See "Clinical features and detection of congenital hypothyroidism".)

●Progressive macroglossia occurs in the mucopolysaccharidoses [38]. (See "Mucopolysaccharidoses: Complications", section on 'Airway obstruction'.)

●Whether a protruding tongue in children with Down syndrome is caused by macroglossia or poor muscular tone is controversial. The tongue surface is papillary and fissured [28]. (See "Down syndrome: Clinical features and diagnosis".)

Symptoms of macroglossia include drooling, speech impairment, difficulty eating, stridor, and airway obstruction [28]. Treatment depends upon severity and ranges from speech therapy in mild cases to surgical reduction [28,39]. Surgical reduction rarely affects tongue mobility or taste [28].

Ankyloglossia — Ankyloglossia, or tongue-tie, occurs when a short lingual frenulum or a tightly attached genioglossus muscle restricts tongue movement (picture 7) [28]. Ankyloglossia is discussed separately. (See "Ankyloglossia (tongue-tie) in infants and children".)

Lingual thyroid — Lingual thyroid tissue may be present at the foramen cecum. Radionuclide scanning will confirm the presence of lingual thyroid tissue and will determine whether any other functional thyroid tissue is present [40]. (See "Clinical features and detection of congenital hypothyroidism", section on 'Thyroid radionuclide uptake and scan'.)

Excision of lingual thyroid tissue should be avoided unless it causes airway obstruction because it may represent the only functional thyroid tissue [41]. If this is the case, the mass of lingual thyroid can be reduced by the administration of thyroid hormone [42,43]. (See "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid", section on 'Lingual thyroid'.)

Median rhomboid glossitis — Median rhomboid glossitis is a well-demarcated, depapillated, pink- to plum-colored patch on the surface of the tongue (picture 11A-B) [28]. The patch ranges from 0.5 to 2 cm wide and from round to rhomboid in shape. Most lesions are found at the location of the embryonic tuberculum impar (just anterior to the foramen cecum), although they may be off center or more posterior. Symptoms of pain, irritation, or pruritus are variable.

Because of its location, median rhomboid glossitis has generally been considered to be a developmental lesion. However, it also appears to be associated with infection (Candida) (picture 12) and diabetes mellitus [44].

For asymptomatic patients, treatment involves observation and follow-up [28]. Symptomatic lesions should be biopsied to exclude carcinoma. Testing for diabetes or immunodeficiency may be warranted.

ORAL CAVITY ANOMALIES — Malformations of the oral cavity may result from errors in the embryonic fusion of the anterior tongue, tongue-base anlagen, and the origin of the thyroglossal duct at the area of the foramen cecum. (See "Soft tissue lesions of the oral cavity in children".)

Cysts and pseudocysts — Cysts and pseudocysts of the major and minor salivary glands are among the most common soft tissue anomalies of the oral cavity. True cysts (which have an epithelial lining) of the floor of the mouth are less common. Thyroglossal duct cysts or primitive foregut cysts occasionally present in the floor of the mouth and may be mistaken for ranulas, which occur more frequently [45,46]. (See "Thyroglossal duct cyst, thyroglossal duct cyst cancer, and ectopic thyroid".)

Mucoceles — Mucoceles are pseudocysts of minor salivary gland origin. They are formed when salivary gland secretions dissect into the soft tissues surrounding the gland. They typically present as smooth swellings in the buccal mucosa near the occlusal plane (picture 13). They can be unroofed, marsupialized, or, preferably, excised in continuity with adjacent minor salivary glands if they interfere with feeding, swallowing, or speech.

Ranulas — Ranulas are pseudocysts associated with the sublingual glands and submandibular ducts. They can be congenital, probably from improper drainage of sublingual glands, or acquired after oral trauma. They appear as blue, fluctuant swellings lateral to the midline in the lower mouth (picture 14) [28].

Large ranulas can present as neck masses if they extend through the mylohyoid musculature of the floor of the mouth (ie, "plunging ranulas") (image 1). Ranulas lack a true cyst wall. As a result, complete excision of the pseudocyst is not necessary. Transoral removal of the sublingual gland is the preferred treatment for both oral and plunging ranulas [47]. Results are comparable, and complications rates are lower with the intraoral approach [48]. Alternatives to sublingual gland resection include marsupialization (creating a permanent fistula from the ranula to the oral cavity) or resection of only the anterior one-half of the sublingual gland, which is the usual source of ranulas [49,50].

Anomalies of the submandibular duct — Anomalies of the submandibular duct, especially atresia of the submandibular punctum, can result in cystic dilation of the duct that resembles a ranula (picture 15) [51]. It is important to differentiate these anomalies as imperforate submandibular dilations can be treated with simple incision and drainage into the mouth (sialodochostomy) and do not benefit from resection of the sublingual gland [52].

Inclusion cysts — Epithelial inclusion cysts may involve the palate or gingival ridges in neonates and infants (picture 16) [28]. They are thought to arise from fusion abnormalities or remnants of minor mucous salivary glands. They appear as single or multiple white or translucent round papules (picture 16). Depending on their location, they carry the eponyms of Epstein pearls (typically seen on the palate) or Bohn nodules (typically seen on the gingival ridges).

Epithelial inclusion cysts are asymptomatic but may cause concern when first noticed by the parents (usually between two and four months of age). No treatment is necessary since they resolve spontaneously over weeks to months [28]. They should be differentiated from eruption cysts and hematomas (picture 17) and natal or neonatal teeth (picture 18). (See "Soft tissue lesions of the oral cavity in children", section on 'Eruption cyst or hematoma' and "Developmental defects of the teeth", section on 'Natal and neonatal teeth'.)

Congenital tumors — A variety of benign congenital tumors can arise in the oral cavity. Teratomas and epithelial choristomas are the most common. In addition, granular cell tumors (eg, epulis, myoblastoma) of the mandibular or maxillary gingiva may be present at birth [53,54].

Choristoma — A choristoma (picture 19) is a mass of normal cells in an abnormal location (ie, heterotopia) [28]. Heterotopic gastric mucosa, enteric duplication cysts (image 2), heterotopic neural tissue, and ectopic cartilage and bone all have been reported in the oral cavity [55-57]. Choristomas may cause feeding difficulty and airway obstruction. Surgical excision is required (picture 20) [28]. Computed tomography (CT) and magnetic resonance imaging (MRI) are helpful in defining the extent of the lesion and preoperative surgical planning [58].

Epulis and other granular cell tumors — Granular cell tumors (eg, epulis, myoblastoma) arise from the mucosa of the gingiva, usually from the anterior part of the maxillary alveolar ridge and typically present as a mass protruding from the mouth that may interfere with feeding or breathing. They are uniformly benign and treated with simple excision.

Epulis occurs exclusively in newborns [28]. Girls are affected 8 to 10 times more often than boys. The lesions range in size from a few mm to 8 cm. Large lesions may interfere with breathing or feeding and require excision (picture 21). Small lesions may spontaneously regress.

NASOPHARYNGEAL ANOMALIES — The nasopharynx is the embryonic intersection of the neural axis, alimentary, and respiratory tracts and is subject to a variety of congenital malformations.

Cystic lesions — Squamous-lined cysts in the midline of the nasopharynx are thought to arise from rests of Rathke pouch [59,60]. Rathke pouch is an ectodermal diverticulum of the primitive nasopharyngeal cavity that forms the anlage of the anterior pituitary.

Thornwaldt cysts — Thornwaldt cysts are midline nasopharyngeal cysts that are thought to arise from obstruction at the Thornwaldt bursa, at the junction of the remnants of the notochord and the pharyngeal ectoderm (image 3). Thornwaldt cysts must be differentiated from nasopharyngeal encephaloceles before excision [61]. Computed tomography (CT) of the nose should be performed to confirm that the skull base is intact, and magnetic resonance imaging (MRI) should be performed to rule out an intracranial connection [62]. (See "Congenital anomalies of the nose", section on 'Nasal encephaloceles'.)

First branchial pouch cysts — The first branchial pouch arises in the pharynx and extends laterally and cephalad to contact the first branchial cleft, forming the Eustachian tube. The pouch and cleft form the inner and outer layers of the tympanic membrane, respectively. First branchial pouch cysts, resulting from errors in embryogenesis, may present in the lateral wall of the nasopharynx [63].

Teratomas — Nasopharyngeal teratomas are principally solid masses composed of tissues derived from embryonic ectoderm, mesoderm, and endoderm. They can be benign or malignant. Teratomas that protrude from the mouth may be diagnosed on prenatal ultrasound and can cause upper airway obstruction in the neonate [64]. A multidisciplinary team, including an otolaryngologist, should be present at birth if a nasopharyngeal teratoma is visualized antenatally. This measure provides the best chance of securing the airway immediately after delivery [65].

Heterotopic brain — Heterotopic brain can be located in the nasopharynx, even in the absence of an encephalocele [66]. Surgical removal, usually by a transpalatal route, has been advocated for diagnosis and relief of upper airway obstruction [67].

Ectopic pituitary — Rarely, functional pituitary tissue may present in the nasopharynx associated with failed closure of the craniopharyngeal canal [68]. A small sella turcica and persistent craniopharyngeal canal can be demonstrated on T1-weighted MRI [69]. MRI usually provides sufficient information to make the diagnosis, and biopsy generally should be avoided in this setting.

PHARYNGEAL ANOMALIES

Second branchial pouch — Second branchial cleft and pouch anomalies are the most common branchial defects [70]. The second branchial pouch originates in the oropharynx. Second branchial pouch anomalies typically present as masses in the oropharynx, which is the site of the palatine tonsils and the embryologic origin of the second branchial pouch [71]. Cysts (image 4), sinuses, and fistulae of the second branchial cleft often can be tracked to the inferior tonsillar pole during resection (picture 22) [72].

Pharyngeal and pharyngolaryngeal bands are a rare cause of obstruction of the upper aerodigestive tract. The associated lack of tonsillar and adenoid tissue in patients with these anomalies suggests that the anomalies may be caused by failed formation of the second branchial arch (figure 1) [73].

Third and fourth branchial arch — The hypopharynx is the source for the third and fourth branchial pouches (figure 1), each arising in the pyriform sinus. Cysts of third or fourth branchial origin present as recurrent abscesses in the neck or simulate suppurative thyroiditis (picture 23).

Preoperative barium esophagography or direct laryngoscopy may reveal an outpouching of the pyriform apex [74]. Failure to follow the tract all the way to the pyriform sinus may result in recurrent cervical infection. Removal of a vertical strip of the posterior thyroid cartilage ala may be necessary to gain adequate surgical access to repair fourth branchial pouch anomalies [75]. Endoscopic cauterization has been advocated to control selected branchial sinuses [76]. (See "Overview of thyroiditis", section on 'Infectious thyroiditis'.)

SUMMARY AND RECOMMENDATIONS

●Micrognathia is a major cause of upper airway obstruction in the neonate due to glossoptosis of the tongue into the airway. The triad of micrognathia, glossoptosis, and a U-shaped palatal cleft describes the Pierre Robin sequence (picture 2A-B). (See 'Jaw anomalies' above and "Syndromes with craniofacial abnormalities", section on 'Pierre Robin sequence'.)

●Congenital anomalies of the lips include clefts, microstomia, macrostomia (transverse facial cleft), lip pits (picture 5), abnormalities of the labial frenula, and synechiae. (See 'Lip anomalies' above.)

●Congenital anomalies of the tongue include cysts (picture 6), mucoceles, macroglossia, ankyloglossia (picture 7), and lingual thyroid. (See 'Tongue anomalies' above.)

●Congenital anomalies of the oral cavity include cysts and pseudocysts (mucoceles, (picture 10), ranulas, (picture 14), Bohn nodules (picture 16) and congenital tumors [eg, choristoma and epulis] (picture 21)). (See 'Oral cavity anomalies' above.)

●Congenital anomalies of the nasopharynx include cysts, teratomas, and heterotopic brain. (See 'Nasopharyngeal anomalies' above.)

●Congenital anomalies of the pharynx are usually related to the second branchial pouch (at the site of the palatine tonsils) and the third and fourth branchial arches (recurrent abscesses in the neck) (figure 1). (See 'Pharyngeal anomalies' above.)