36 Craniofacial microsomia

Joseph G. McCarthy, Barry H. Grayson, Richard A. Hopper, Oren M. Tepper

Synopsis

Patients with craniofacial microsomia (CFM) require the care of a skilled multidisciplinary clinical team.

Phenotypic features of CFM are highly variable. While the three structures most commonly affected include the auricle, mandible, and maxilla, abnormal development can occur in any of the derivatives of the first or second branchial arches.

During the evaluation of CFM, it is essential to assess for retroglossal airspace narrowing and obstructive sleep apnea via endoscopy and sleep studies, particularly in bilateral cases.

Distraction osteogenesis (DO) of the mandible should be considered in neonates and infants with CFM who exhibit severe respiratory compromise and who may otherwise require a tracheostomy.

Vectors of mandible distraction (vertical, oblique, or horizontal) should be planned according to treatment goals.

In cases of severe mandibular hypoplasia, staged procedures with grafting (nonvascularized or vascularized bone) should be performed, often followed by DO.

If two-jaw surgery is to be performed for CFM, a two-splint (intermediate splint) technique is used and the technique is usually deferred until skeletal maturity has been achieved.

Orthodontic monitoring is important throughout the years of growth and development. Interventions are especially important during and after the distraction process to prevent undesired movements (i.e., anterior open bite, lateral shift) and in the period surrounding two-jaw surgery.

The clinical association of ipsilateral congenital mandible and ear anomalies was first described in 1861. Since that time, various names have been used to designate this condition: first and second branchial arch syndrome, otomandibular dysostosis, oculoauriculovertebral sequence, Goldenhar syndrome, hemifacial microsomia, and CFM. Because the dysmorphology can be bilateral in 5–30% of cases, the terms unilateral and bilateral CFM are preferred. Goldenhar syndrome or oculoauriculovertebral sequence is a variant of CFM, constituting approximately 10% of patients. It is differentiated by the presence of ocular abnormalities (lipoma, lipodermoid, epibulbar dermoid, or coloboma) and cervical spine anomalies.

Basic science/disease process

Incidence

The reported incidence of CFM ranges from 1 in 3500 to 1 in 26 550 live births, with a commonly quoted incidence of 1 in 5600 live births. When one considers the presence of congenital ear tags and mild unilateral mandibular hypoplasia, the incidence is obviously much higher. It is the second most common craniofacial anomaly after cleft lip and palate.

Grabb reported a male predominance, with a male-to-female ratio of 63 : 39, and Rollnick reported a similar ratio of 191 : 103. The clinical series of Horgan et al. reported an equal sex ratio of 59 males to 62 females.

Etiopathogenesis

The underlying cause or etiopathogenesis of CFM remains a subject of debate. The prevailing theory was that CFM was a sporadic event, possibly precipitated by exposure to teratogens. Other studies have instead suggested a fundamental role for genetic transmission in some patients. The etiology of CFM is probably heterogeneous among individuals, with variable contributions from extrinsic and intrinsic factors. Support for a teratogenic etiology of CFM is based largely on animal studies. Poswillo exposed mouse embryos to triazine by maternal administration of the drug, causing CFM-like phenotypes (Fig. 36.1). Focal hematomas arising from disruption of the stapedial artery were also observed. Although a “stapedial artery hemorrhage etiology” is attractive because the vessel is a second branchial arch derivative, a causative association between the bleeding and the deformities has not been made. The hemorrhages occurred 14 days after administration of the teratogen, and there was no clear temporal relationship between the hemorrhage appearance and the associated phenotypic deformity. When mice are exposed to triazine later in development (10 days of gestation), all animals developed deformities; however, only a third showed evidence of a hematoma. The authors concluded that triazine has a direct teratogenic effect and the stapedial artery findings were simply a side-effect. In contrast to those described by Poswillo, these animals demonstrated more evidence of bilateral deformities and inner-ear anomalies. Intermittent occlusion of the internal carotid system of fetal sheep late in gestation has been shown to result in deformities similar in appearance to CFM. The vascular disruption hypothesis, therefore, cannot be excluded.

Fig. 36.1 Mouse phenocopy of craniofacial microsomia induced by the administration of triazine. (A) Histologic section of the head showing bilateral hematomas. The smaller one is in the ear region (right), and the large one encompasses the ramus and angle of the mandible (left). (B) Upper panel, normal ear–jaw relationship at full term in the normal animal. Lower panel, the diminutive helix and abnormal mandible in the unilateral craniofacial microsomia phenocopy.

(Reproduced from Poswillo D. The pathogenesis of the Treacher–Collins syndrome [mandibulofacial dysostosis]. Br J Oral Surg. 1975;13;1.)

Rats exposed to etretinate, a retinoic acid derivative, show deformities comparable to the first and second branchial arch syndromes. This finding is consistent with the finding that neural crest cells express large amounts of retinoic acid-binding proteins. Furthermore, when retinoic acid is administered early in development, it interferes with cell migration. When administered later in gestation, however, retinoic acid kills ganglionic placodal cells, resulting in a deformity similar to mandibulofacial dysostosis (Treacher–Collins).

Human case studies also support a teratogen-based etiology for CFM. Thalidomide and ethanol administration during pregnancy and gestational diabetes are exogenous other factors that have been implicated.

Support of a genetic etiology of CFM has come from both animal and human studies. A transgenic mouse model for CFM with an insertional deletion on mouse chromosome 10 has been described with an autosomal-dominant mode of transmission and 25% penetration. The affected animals display low-set ears, unilateral microtia, and jaw asymmetry, without evidence of middle-ear abnormality. Second branchial arch hematomas were also observed in the embryos.

Human genetics studies have documented a positive family history in 9.4% of 32 probands, 21% of 57 probands, 26% of 88 probands, and 44% of 82 probands. Kaye et al. performed segregation analysis on 74 families of probands with CFM and rejected the hypothesis that genetic transmission is not a causative factor. The evidence favored autosomal-dominant inheritance; however, recessive and polygenic models were not distinguishable. Despite the suggestion of autosomal-dominant transmission, they found only a 2–3% overall recurrence rate in first-degree relatives. This figure compares to the 10% recurrence risk in first- and second-degree relatives reported by the same group in an earlier study of 294 individuals with CFM. Graham et al. described a family with a strong autosomal-dominant transmission of Goldenhar-like phenotype with linkage to a mutation at locus 8q13.

The high variability and low penetrance of CFM may be explained in terms of genetic transmission by a number of theories. Compensation of defective genes by adjacent normal genes has been described in a cleft palate mouse model, and it may explain the variability of CFM. Another mechanism may be “maternal rescue,” a mechanism by which transplacental transfer of a normal maternal gene product may compensate for an abnormal fetal gene. The low penetrance of CFM may be explained by differential expression of maternal and paternal DNA sequences (genomic imprinting) or by only a limited number of cells possessing the abnormal gene (mosaicism).

Studies on the incidence and expression of craniofacial anomalies in twins have provided insight into the etiology of CFM. Mulliken’s group described 10 twin pairs with CFM. Only one of the pairs, who were monozygotic, was concordant for the anomaly. Other twin studies have noted a high level of discordance of CFM among monozygotic twins. Even among concordant monozygotic twins, the anomaly can be mirror image. One theory to explain the discordant findings is that vascular insufficiency of the first and second branchial arch occurs in monozygotic twins with a shared placenta (monochorionic) and unequal circulation. Arguing against this is the observation that discordance is not limited to monochorionic twins but is also observed in dichorionic pairs. Monozygotic discordance would appear to refute the teratogen theory of CFM; however, monozygotic twins have been reported to respond to in utero teratogens in a discordant manner.

In summary, the exact etiology of CFM is not known. It is likely to involve a number of factors ranging from abnormal genes with various intrinsic modifiers to extrinsic insults such as teratogens or vascular events. It is also probable that, as in patients with cleft palate, the population of patients with CFM is a heterogeneous group. Some individuals with the phenotype may be part of a family with a dominant abnormal gene expression, in which case the recurrence risk would approach 50%. In other individuals with a purely environmental etiology, recurrence would be negligible. The empirically stated recurrence rate of 2–3% for CFM should be recognized as a group summary and placed in context when an individual or family with this phenotype is counseled.

Embryology

The ear serves as a frame of reference in this syndrome because of its developmental relationship with the jaw. A brief review of the phylogeny and ontogeny of the auricle and hearing apparatus is helpful in understanding the embryogenesis of the malformation in the patient with CFM.

The two principal divisions of the organ of hearing are derived from different embryonic anlagen. The sensory organ in the inner ear is derived from the ectodermal otocyst; the sound-conducting apparatus in the external and middle ear comes from the gill structures.

The membranous labyrinth has its beginning in the -week-old human embryo as a thickening of the ectoderm in the side of the head – the otic placode. This area is enfolded to become the otic pit and is subsequently pinched off to become the otocyst. By means of a series of folds, the otocyst differentiates in the 3-month-old fetus into the endolymphatic duct and sac, the semicircular endolymphatic ducts, the utricle, the saccule, and the organ of Corti. By the fifth month of fetal life, the sensory end organ of the ear attains adult form and size as the cartilaginous otic capsule ossifies.

It is speculated that the aquatic ancestors of humans swam in seas not yet as salty as today’s oceans and that endolymph, entrapped by the enfolding otocyst, closely resembles in chemical composition the dilute salt water of the primeval sea. Our ancient aquatic forebears did not require any special mechanism to transmit sound to the inner ear. As in today’s fish, sound was readily transmitted from the sea through the skin to the fluid of the inner ear.

When these ancestors struggled out of the seas on to dry land, a new problem appeared. A mechanical device was needed to convert air vibrations of large amplitude and small force into fluid vibrations of small amplitude and large force. The gill structures, no longer needed for breathing, became converted into such a mechanism. The first branchial groove became the external auditory meatus and canal; the first pharyngeal pouch became the eustachian tube and middle ear. Instead of the branchial groove and pharyngeal pouch connecting to become a gill cleft, a thin intervening layer of tissue remained to form the tympanic membrane.

The mandible, incus, and malleus develop from the cartilage of the first branchial arch (Meckel cartilage) (Fig. 36.2). The stapes (with the exception of the footplate, which originates from the otic capsule), styloid process, and hyoid bone develop from the cartilage of the second branchial arch (Reichert cartilage). The large area of the tympanic membrane, connected by the lever system of the ossicular chain to the small area of the oval window, provides the ear with an effective mechanism to overcome the sound barrier between air and water.

Fig. 36.2 Schematic drawing: the visceral arch cartilages appear in green; the cranial base cartilages appear in purple. The remaining skeletal elements are the intramembranous bones of the face and cranial vault (blue).

(Adapted from Hamilton WJ, Mossman H. Human embryology, 4th ed. Cambridge, England: W. Heffer; 1972.)

By the third fetal month, the external auricle has been formed from the first and second branchial arches on either side of the first branchial groove, which is the primary shallow, funnel-shaped external auditory meatus (Fig. 36.3). From the inner end of the primary meatus, a solid cord of ectodermal cells extends farther inward, with a bulb-like enlargement adjacent to the middle ear. It is not until the seventh fetal month that the cord canalizes, beginning medially to form the tympanic membrane and extending laterally to join with the primary meatus to form the completed external auditory meatus. The external and middle ears, although capable of transmitting sound to the inner ear, are not yet of adult form and size.

Fig. 36.3 Comparison of external ear development in the mouse (upper panel), on which most experimental studies have been conducted, and the human (lower panel). The various growth centers (auricular hillocks, which are six in number) are virtually the same in the two species.

(Reproduced from Jarvis BL, Sulik KK, Johnston MC. Congenital malformations of the external, middle, and inner ear produced by isotretinoin exposure in fetal mouse embryos. Otol Head Neck Surg. 1990;102;391–401.)

In the seventh fetal month, pneumatization of the temporal bone begins. At birth, the eustachian tube inflates; the fetal mesoderm tissue in the middle ear and antrum continues to resorb until the epithelium lies close to the periosteum, and pneumatization of the temporal bone proceeds.

The external auditory meatus, entirely cartilaginous at birth (except for the narrow incomplete ring of the tympanic bone), deepens by growth of the tympanic bone to form the adult osseous meatus. Except for pneumatization of the petrous apex, which may continue into adult life, the external and middle ears finally attain adult form and size in late childhood (in contrast to the inner ear, which becomes adult in fetal life). It is generally accepted that the first branchial arch furnishes the anterior part of the auricle; the second arch provides the structures of the remaining external ear.

The maxilla, palatine bone, and zygoma develop from the maxillary process of the first branchial arch, whereas the mandible forms from the mandibular process. Meckel cartilage, the primary jaw of lower vertebrates, represents the temporary skeleton of the first pharyngeal arch; the two symmetric cartilaginous bars describe a parabolic arch that serves as a model and guide in the early morphogenesis of the mandible.

Three main regions of Meckel cartilage should be considered: (1) the distal portion, which becomes incorporated into the anterior part of the body of the mandible; (2) a middle portion, which gives rise to the sphenomandibular ligament and contributes to the mylohyoid groove of the mandible; and (3) the proximal or intratympanic portion, which differentiates into the malleus, the incus, and the anterior malleolar ligament.

Pathology

A fundamental characteristic of the syndrome is the variable manifestation of the pathologic findings.

The deformity in CFM usually has the three major features of auricular, mandibular, and maxillary hypoplasia. The hypoplasia, however, can also involve adjacent anatomic structures: the zygoma, the pterygoid processes of the sphenoid bone, the temporal bone (the middle ear; the mastoid process is small and acellular), the frontal bone, the facial nerve, the muscles of mastication, the parotid, the cutaneous and subcutaneous tissues, the tongue, the soft palate, the pharynx and the floor of the nose.

Whereas the jaw and ear deformities are the most conspicuous in the majority of patients, the first and second branchial arches and the structures derived from them are intimately interlinked with the chondrocranium and membranous bones of the skull; associated deformities of the temporal bone and other cranial bones are inevitable. In extreme forms of the dysplasia, widespread craniofacial involvement is evident (Fig. 36.4). As Pruzansky stated, maldevelopment in one area may trigger a “domino effect,” with involvement of the entire craniofacial skeleton including microphthalmos, orbital dystopia, and orbitofacial clefts.

Fig. 36.4 Variable clinical manifestations of unilateral craniofacial microsomia. (A) Mild example characterized by microtia, canting of the oral commissure and alar base plane, deficiency of the affected cheek soft tissues, and deviation of the chin to the affected side. (B) Moderate example. Note the microtia, deficient cheek soft tissue, macrostomia, canting of the oral commissure, and retruded and deviated chin. (C) Severe example with microtia, microphthalmos, retrusion of the brow, occlusal cant, elevation of the oral commissure, and deviation of the chin.

Skeletal tissue

The most conspicuous deformity of unilateral CFM is the hypoplasia of the mandible on the affected side. The ramus is hypoplastic or even absent, and the body of the mandible curves upward to join the vertically reduced ramus. The chin is deviated to the affected side. On the “normal” or “less affected” side, the body of the mandible is also characterized by abnormalities in the skeletal and soft-tissue anatomy. The body of the “normal” mandible shows an increased horizontal dimension and an increase in the gonial angle. The increase in length of soft- and hard-tissue structures on the less affected side may represent compensatory growth, secondary to the growth deficiency on the affected side.

Ramus and condyle malformations vary from minimal hypoplasia or blunting of the condyle to its complete absence in association with hypoplasia or agenesis of the ramus (Fig. 36.5). In all patients, condylar anomalies can be demonstrated, and this finding may be pathognomonic of the syndrome. As a consequence, the spatial relationships of the malformed or deficient skeletal parts, as well as the associated neuromuscular components, become of paramount importance in the diagnosis and planning of treatment.

Fig. 36.5 Three-dimensional computed tomography scans of three unilateral craniofacial microsomia cases demonstrating increasing severity as viewed from left to right. The affected side of each case is on the top panel, with the corresponding normal or contralateral side on the lower panel. The three cases correspond to the Pruzansky classification of mandibular deformity described later in the chapter: class I (left), class II (center), class III (right).

The posterior wall of the glenoid fossa is partially formed by the tympanic portion of the temporal bone, which provides the bony portion of the external auditory canal in the normally developed ear. When there is hypoplasia of the temporal bone, the posterior wall of the glenoid fossa cannot be identified. The infratemporal surface is flat, and the hypoplastic ramus is often hinged on this flat surface at a point anterior to the contralateral “unaffected” temporomandibular joint.

Mandibular growth deficiency usually is closely related to the degree of hypoplasia of the condyle. In more severe conditions there is considerable disparity in condylar growth between the affected and contralateral sides. The cant of the occlusal plane (higher on the affected side) is caused by the short, hypoplastic ramus and by hypoplasia of the ipsilateral maxillary dentoalveolar process (Fig. 36.6). The floor of the maxillary sinus and of the nose on the affected side is canted at a higher level. In some patients, the base of the skull is elevated on an inclined plane similar to the inclined occlusal plane. Anteroposterior and superoinferior dentoalveolar and skeletal dimensions are reduced on the affected side. Crowded dentition, with a characteristic tilt of the anterior maxillary and mandibular occlusal planes upward on the affected side, is often noted.

Fig. 36.6 Patient with left-sided craniofacial microsomia demonstrating the characteristic occlusal and nasal cant upward on the affected side along with associated cheek hypoplasia and ear anomaly.

Craniofacial bones other than the mandible or maxilla can be involved, especially the tympanic and mastoid portions of the temporal bone; the petrous portion usually is remarkably spared. The styloid process is frequently smaller on the affected side. The mastoid process can have a flattened appearance, and there can be partial or complete lack of pneumatization of the mastoid air cells (Fig. 36.7).

Fig. 36.7 Computed tomography scan images of condylar and temporal abnormalities in unilateral craniofacial microsomia compared with the contralateral side. Upper panel, axial cuts through the temporal bone at the level of the condylar head. Upper left, on the less affected side, normal lateral location of the glenoid fossa and pneumatization of the mastoid bone are visualized. Upper right, on the affected side, the glenoid fossa and condylar head are medially displaced, and there is an absence of air cells in the mastoid bone. Lower panel, coronal cuts through the condylar and temporal bone. Lower left, on the less affected side, there is normal condylar morphology with level articulation with the temporal bone. Lower right, on the affected side, the condylar head is dysmorphic and articulates with the temporal bone at an angle.

The zygoma can be underdeveloped in all its dimensions, with flattening of the malar eminence. A decrease in the span of the zygomatic arch results in a decrease in the length of the lateral canthal–tragal line on the affected side.

Disparities in the vertical axis of the orbit can be seen, with or without evidence of microphthalmos (Fig. 36.8). Often in this situation, there is flattening of the ipsilateral frontal bone – an appearance of plagiocephaly without radiographic evidence of coronal synostosis.

Fig. 36.8 (A) Craniofacial microsomia with orbital and frontal bone involvement (right side). There is vertical orbital dystopia. (B) The congenital fronto-orbital asymmetry persists even after cranial vault remodeling.

Nonskeletal (soft) tissue

The relationship between the soft tissue and skeletal dysmorphology of CFM is not fully understood. One theory is that they are independent manifestations of the same genetic or environmental event. Another possibility is that one is primarily involved, whereas the other is only a secondary event.

The “functional matrix” theory of Moss attributes the overall growth and development of the head to the development of the soft-tissue matrix and functional spaces. The matrix is composed of cells, tissues, organs, and air volumes that serve a functional role. The associated “hard” tissues, such as bone and cartilage, serve to protect and support the functional matrix. Their morphology is solely determined by the functional matrix. As summarized by Moss, “bones do not grow, they are grown.” This theory has been supported by animal research examining the effect of transposition of muscles of mastication on bone morphology. Investigation of the effect of soft tissue on bone shape in humans with unilateral CFM has been limited to computed tomographic (CT) analysis. Results of these studies do suggest that changes in the muscles of mastication can elicit a postnatal change in bone morphology but that the opposite – bone changes affecting muscle – does not take place (Fig. 36.9). It can be speculated that, if the functional matrix theory is validated, future treatment of CFM may be limited to early manipulation of the soft-tissue matrix to elicit a secondary effect on the associated bone.

Fig. 36.9 Top panel, computed tomography (CT) images of a child with unilateral (left) craniofacial microsomia and grade I Pruzansky mandible. The images show composites of the osseous surface and segmented masticatory musculature derived from CT data. Bottom panel, images of a child with unilateral (right) craniofacial microsomia and grade III Pruzansky mandible. CT images show composites of the osseous surface and segmented masticatory musculature derived from CT data.

(Courtesy of Drs. Alex Kane and Jeffrey Marsh, Washington University, St. Louis.)

Muscles of mastication

Muscle function, especially that of the lateral pterygoid muscle, is impaired in many patients with CFM. The right muscle is responsible for the lateral movement of the mandible to the left side, whereas the left muscle controls movement to the right. Both sides act synergistically in executing protrusive opening movements. In patients with CFM, a severe limitation of protrusive and lateral movements secondary to hypoplasia of the lateral pterygoid muscle is observed.

The impact of this factor is apparent both on the developing musculature and on the morphology of the attached bone. An alteration in mandibular movements (opening, lateral, and protrusive) comparable with the degree of mandibular deficiency is often noted.

When the patient opens the mouth, the deviation toward the affected side is produced not only by the skeletal asymmetry but also by the minimal or absent contribution of the ipsilateral medial and lateral pterygoid muscles in countering the opposing actions of the muscles on the unaffected side. The condyle on the less affected side is displaced abnormally downward and laterally when the mandible is depressed, almost to the point of dislocating the condyle from the glenoid fossa. No discernible condylar movement can be elicited on the affected side during opening and protrusive movements of the mandible. Thus, in testing for lateral pterygoid muscle weakness, one finds an inability to shift the jaw laterally toward the unaffected side and to deviate the midline of the chin toward the affected side during opening and during forceful protrusion.

In many cases, the coronoid process is absent, and there is reduction in the size of the temporalis muscle. The associated masseter and medial pterygoid muscles are also grossly deficient.

Ear

Auricular malformations are a usual manifestation of the syndrome. Meurman proposed a classification of the auricular anomalies based on the studies of Marx (1926): grade I, distinctly smaller malformed auricles with most of the characteristic components; grade II, vertical remnant of cartilage and skin with a small anterior hook and complete atresia of the canal; and grade III, an almost entirely absent auricle except for a small remnant, such as a deformed lobule (Fig. 36.10).

Fig. 36.10 Example of three grades of auricular anomalies in the Meurman classification. (A) Grade I: small malformed ear with most components present. (B) Grade II: vertical remnant of skin and cartilage. There is atresia of the external auditory meatus. (C) Grade III: the auricle is almost entirely absent except for a misplaced lobule and diminutive skin and cartilage remnants.

In a comprehensive study, Caldarelli et al., using air and bone conduction audiometry and temporal bone tomography, evaluated 57 patients with CFM. It was observed that the degree of Meurman auricular deformity does not correlate exactly with hearing function. The type of hearing loss, although usually assumed to be conductive in origin, can be determined only by audiometry. Tomography, not auricular morphology, is the only indicator of middle-ear structure. The unaffected ear may also harbor abnormalities in structure and function and should be evaluated.

Congenital hearing loss may be due to a malformed inner ear, hypoplasia of the cochlear nerve and brainstem auditory nuclei, or hypoplasia and impaired function of cranial nerves IX through XII.

Nervous system

A wide variety of cerebral anomalies exist in CFM and may include ipsilateral cerebral hypoplasia, hypoplasia of the corpus callosum, hydrocephalus of the communicating type and obstructive type, intracranial lipoma, and hypoplasia and impression of the brainstem and cerebellum. Other associated abnormalities include cognitive delay, epilepsy, and encephalographic findings suggestive of epilepsy.

Cranial nerve abnormalities are frequent in CFM and can range from arhinencephaly of the bilateral type and unilateral type to unilateral agenesis and hypoplasia of the optic nerve with secondary changes in the lateral geniculate body and visual cortex, congenital ophthalmoplegia and Duane retraction syndrome, hypoplasia of the trochlear and abducens nuclei and nerves, congenital trigeminal anesthesia, and aplasia of the trigeminal nerve and motor and sensory nucleus.

The most common cranial nerve anomaly is facial paralysis secondary to agenesis of the facial nerve in the temporal bone or hypoplasia of the intracranial portion of the facial nerve and facial nucleus in the brainstem. Any cranial nerve can be clinically involved in patients with CFM, and it is likely that hypoplasia or agenesis of a portion of the entire cranial nerve trunk and corresponding brainstem nuclei represents the pathoanatomic substrate of the clinical dysfunction. In the clinical setting the most common finding is dysfunction of the marginal mandibular nerve on the affected side.

Skin and subcutaneous tissue

The deficiency of soft tissues on the affected side in CFM is evident from the reduced distance between the mastoid process and the oral commissure or lateral canthus of the eye. The skin and subcutaneous tissue show varying degrees of hypoplasia, particularly in the parotid-masseteric and auriculomastoid areas. Hypoplasia or aplasia of the parotid gland can place the branches of the facial nerve in a superficial and surgically vulnerable position.

In the series of patients described by Grabb, 10% had malformations of the eyes and eyelids or palate. Transverse facial clefting, ranging from macrostomia to a full-thickness defect of the cheek, can be present (Fig. 36.11). The clefts probably result from a failure of the maxillary and mandibular processes to fuse. In embryonic development, the lateral commissure of the oral fissure is initially situated at the point of bifurcation of the maxillary and mandibular processes. With fusion of these and development of the muscles of mastication, the original broad mouth is reduced in size. In addition, the parotid glands, originally located near the embryonic oral commissure, grow laterally toward the developing ear, but the parotid duct papillae remain in their more medial position.