Jeffrey C. Posnick, DMD, MD

Inheritance Pattern

The occurrence of HFM has been estimated to range from 1 in 3500 to 1 in 26,550 live births. Cohen suggests that the birth prevalence is likely to be around 1 in 5600 live births.62,26 Morrison and colleagues stated a prevalence rate of conditions on the oculo–auriculo–vertebral spectrum of 1 in 45,000 in Northern Ireland.²⁶

Kelberman and colleagues performed a genome-wide search for linkage in two families with features of hemifacial microsomia.¹⁰⁵ In one of these families, the data were highly suggestive of linkage to a region of approximately 10.7 cM on chromosome 14q32, with a maximum multipoint LOD score of 3.00 between microsatellite markers D14S987 and D14S65. Linkage to this region was excluded in the second family, thereby suggesting genetic heterogeneity. With the use of an animal model.

Poswillo demonstrated that early vascular disruption with expanding hematoma formation in utero resulted in the destruction of differentiating tissues in the region of the ear and the jaw.214–218 The degree of local destruction appeared to be related to the severity of tissue damage caused by the hematoma. The constellation of anomalies seen in patients with HFM suggests an origin that occurs at about 30 to 45 days’ gestation. Naora and colleagues described a transgenic mouse line that carried an autosomal dominant insertion mutation that resulted in facial anomalies that resemble HFM, including microtia and abnormal occlusion.¹⁶⁴

First and second branchial arch malformations similar to HFM have been observed in infants who are born to women who have been exposed to thalidomide and primidone. The administration of isotretinoin (Accutane) may also injure neural crest cells and prevent their normal development, thereby resulting in hemifacial hypoplasia similar to that observed in patients with HFM. It has been documented that acute exposure to ethanol during gastrulation (i.e., the transformation of the blastula into the gastrula) may induce asymmetric facial development.

Discordance in monozygotic twins has been frequently reported. Concordance with variable expression has also been rarely documented in monozygotic twins. The rarity of the reports of the concordance of the malformation in twins supports the suggestion that the condition is sporadic in most families. Familial instances have been observed with variable expressivity. Overall, the empiric recurrence risk is on the order of 2% to 3%; however, 1% to 2% of cases suggest an autosomal dominant inheritance pattern.

Engiz and colleagues reviewed the clinical and laboratory findings of 31 individuals with Goldenhar syndrome (15 boys and 16 girls) between the ages of 1 day and 16 years.⁴⁷ The characteristic features were preauricular skin tags (90%), microtia (52%), hemifacial microsomia (77%), and epibulbar dermoids (39%). Vertebral anomalies were noted in 70%, cardiac malformations were found in 39%, genitourinary anomaly were noted in 23%, and various central nervous system malformations were found in 47%.

Several classification systems for HFM have focused on one or more fundamental anatomic features of this anomaly. In 1991, Vento and colleagues described the OMENS classification for HFM. This system substratifies each of five anatomic manifestations of HFM in accordance with their dysmorphic severity on a scale from 0 to 3. The five manifestations each constitute one letter of the OMENS acronym: orbital asymmetry; mandibular hypoplasia; ear deformity; nerve dysfunction; and soft-tissue deficiency. Scoring was done on the basis of conventional radiographs (e.g., posteroanterior, lateral, submental, panoramic), physical examinations, and photographs. Although the OMENS classification does allow for the objective cataloguing of a range of the abnormalities that constitute the spectrum of HFM, it falls short in terms of providing effective communication when determining the timing and technique that are best suited for the reconstruction of each component of the anomaly (i.e., maxillo-mandibular, orbito–zygomatic, soft tissues, external ear). It also is of limited value with regard to overall patient management.²⁷⁶

At the present time, HFM should be regarded as a nonspecific symptom complex that is etiologically and pathogenetically heterogeneous.* Extreme variability of expression is the characteristic finding.

Considerations during Infancy and into Early Childhood

At the time of birth, for a child with HFM, concerns will center on the adequacy of the airway; swallowing and feeding; hearing; vision; the presence of other associated malformations; and family unit psychosocial issues.3,16,27,28,56,57,112,125,131,165,175,193,196,197,199,207,208

The airway may be compromised as a result of 1) maxillary hypoplasia with choanal (nasal) obstruction 2) mandibular micrognathia with a retropositioned tongue obstructing the oropharyngeal/hypopharyngeal spaces 3) laryngomalacia/tracheomalacia or 4) neuromotor involvement.3,16,27,28,57,195 Depending on the severity of these malformations, a spectrum of airway problems may be present and necessitate treatment that ranges from special infant positioning with an extended hospital stay to mandibular osteotomies with advancement; on rare occasions, immediate or delayed tracheostomy may be required.

When the airway is compromised, the newborn has difficulty swallowing enough fluids and taking in enough calories (i.e., maintaining hydration and positive nitrogen balance) while simultaneously breathing effectively (i.e., sufficient oxygenation). In this situation, gavage-assisted feedings or the placement of a gastrostomy tube may be necessary to ensure adequate nutrition without aspiration or respiratory distress.

When a cleft (of the lip, palate, or both) or macrostomia is present, the timing of correction of these anomalies is generally similar to that used for the patient with non-syndromic cleft lip and palate (Fig. 28-1).

Soon after birth, examination by a medical geneticist and the procurement of a blood sample for chromosomal studies (i.e., genetic analysis) will help to discern the extent of birth defects and the risk of recurrence. Evaluation by the pediatric otolaryngologist in combination with the speech and feeding specialist will clarify the extent of breathing, swallowing, and feeding difficulties. Initial audiologic testing via auditory evoked brain responses is essential to clarify neurosensory hearing function. A pediatric ophthalmologic assessment is useful to assess extraocular muscle function, corneal exposure difficulties, visual potential, and adnexal region malformations.

When moderate to severe skeletal malformations are present, a craniofacial computed tomography (CT) scan from the top of the skull through the cervical spine with three-dimensional reformation will be useful to document the extent of craniofacial skeletal dysmorphology. A focused petrous temporal bone CT scan is also required to document external auditory canal anatomy as well as middle and inner ear anatomy. Because of the potential increased risk of radiation exposure to infants, these imaging studies may be delayed until they are necessary for surgical treatment planning. Appropriate craniofacial, maxillofacial, cleft lip and palate, and auricular reconstructive surgeons should also be consulted as indicated.

Dysmorphology Associated with Hemifacial Microsomia

Facial Growth Potential with Hemifacial Microsomia

The potential for longitudinal facial growth in a child who is born with HFM is an important factor when considering the timing and techniques of reconstruction.96,97,114,115,133,144–147,152–154,168,194,202–204,225,226,230–232 An additional pivotal consideration for the maxillofacial reconstruction of the individual with HFM is the integrity of the glenoid fossa–condyle–ascending ramus of the mandible (Fig. 28-4). Some authors speculate that a reduced mandibular growth potential secondarily leads to the observed maxillary deficiency on the ipsilateral side with progressive canting of the occlusal plane. Those who advocate mandibular surgery during the mixed dentition often do so with the belief that it will effectively correct the lower jaw malformation and that normal ongoing mandibular growth will continue with the prevention of secondary maxillary growth deformities in an otherwise normal upper jaw. There are objective clinical and radiographic studies in the literature that review the issue of the progression of deformity with HFM during growth.^{87–89,194,225,226}

Rune and associates placed metallic implants in the jaws to study the facial growth of 11 patients with HFM.225,226 They collected and studied serial roentgen stereophotogrammetry images from each patient. They found that, in five patients, the cant of the occlusal plane seemed to “slightly” increase; in the remaining six patients, the occlusal plane asymmetry either remained the same or improved with time. The authors also stated that the pattern of mandibular displacement showed no correlation with the severity of the presenting deformity. They concluded that the data “do not support the claim that the asymmetry of the jaws is invariably increased in time because of growth disparity between the affected and the unaffected sides.”^225,226

Polley and associates completed a longitudinal radiographic cephalometric study of the maxillofacial region in patients with HFM.¹⁹⁴ Twenty-six patients were included in the study and were followed longitudinally. Five patients (19%) had a Pruzansky grade I mandibular deformity, 14 patients (54%) had a Pruzansky grade II deformity, and 7 patient (27%) had a Pruzansky grade III deformity. The average age at the time that the initial cephalometric records for all patients were obtained was 3.5 years (range, 0.7 to 9.2 years), and the average age at the time that the final cephalometric records were obtained was 16.7 years (range, 10.1 to 22.5 years). None of the study patients had undergone surgical or orthopedic jaw manipulation during the time of the study, although nine patients underwent fixed appliance orthodontic treatment. Vertical and horizontal skeletal mandibular asymmetry was evaluated with posteroanterior cephalometry. The authors found that the growth of the affected side in patients with HFM parallels that of the contralateral side. The degree of mandibular asymmetry in the study patients remained relatively constant throughout craniofacial development. The mandibular skeletal deformity as measured in the study subjects did not progress with time. The growth rate of the affected side was similar to that of the contralateral side in each subject, irrespective of the degree of presenting mandibular deformity on the involved side. In the study group, subsequent growth occurred in both mandibular rami in each patient. This was true for all patients, irrespective of the Pruzansky grade and the side of the mandible that was affected.

Meazzini and colleagues conducted a long-term facial growth study of children affected by HFM with Type I or Type II mandibular malformations.^136A The study group (N = 8) was not subjected to any treatment until adulthood. With the use of the panoramic radiograph analysis of ramus vertical heights, data confirmed that facial proportions in patients with HFM were maintained throughout growth when no treatment was undertaken. The authors concluded that HFM does not progress in the degree of facial asymmetry or deformity when left to mature naturally.

Ongkosuwito and colleagues studied mandibular growth in 84 consecutive patients with a confirmed diagnosis of unilateral HFM. The mandibular malformation for each subject was categorized into one of four grades on the basis of the Pruzansky/Kaban classification. The malformations were then regrouped to reflect those with a functional glenoid fossa and condyle (Type I and Type IIA) and those without (Type IIB and Type III). The study groups were compared with a normal age-matched Danish control group. For each subject, an orthopantomogram was obtained and used to perform measurements of ramal height (i.e., the distance measured in millimeters between the condylion and the gonion) on each side. The data confirmed that patients with HFM start with a shorter ramal height and end up with a shorter ramal height, although growth is the same in both patients with HFM (regardless of the extent of malformation) and controls. In patients with HFM, the ramal height is smaller on both sides, which means that growth is characterized not simply by unilateral underdevelopment but by a complex three-dimensional phenomenon.^161A

According to the independent findings of Polley and colleagues, Rune and colleagues, Meazzini and colleagues, Ongkosuwito and colleagues, the mandibular asymmetry associated with HFM is not progressive. In these studies, progressive canting of the maxillary plane was not routinely observed (Figs. 28-5 through 28-7).

An alternative perspective is presented by Kaban and colleagues.92,93,95 Their research suggests to them that, as a result of ongoing growth after birth in patients with HFM, there is progressive canting measured at the pyriform rims, the occlusal plane, and the intergonial angles, especially with the Type IIB and III mandibular malformations. The authors recommend that mandibular reconstruction during the mixed dentition be considered to correct the lower jaw deformity in anticipation of normal ongoing longitudinal growth; to prevent secondary maxillary deformities (in an otherwise normal maxilla); and to alleviate psychosocial issues that would otherwise occur during childhood. I believe that Kaban and colleagues’ rationale for first-stage mandibular reconstruction during the mixed dentition in children with HFM are overly optimistic.

Classification of Temporomandibular Joint–Mandibular Malformation

The extent of temporomandibular joint (TMJ)–mandibular deficiency is an important factor when considering the timing of and techniques for reconstruction.108,118,119,249 Imprecise definitions of the degrees of TMJ–mandibular anomalies have resulted in miscommunication among clinicians and in the literature. In an article published during the late 1960s, Pruzansky classified the presenting mandibular anomalies of HFM into three grades (Type I through Type III) in accordance with the extent of hypoplasia of the mandibular condyle and ramus.²²⁰ Kaban and colleagues refined the Pruzansky classification to further clarify the degree of glenoid fossa–condyle–ascending ramus malformation observed in patients with HFM.^94,157 The Kaban classification provides an excellent starting point for defining the reconstruction required in each individual patient (see Fig. 28-4).

A Type I mandible has only a minimal degree of hypoplasia of the glenoid fossa, the condyle, and the ascending ramus (see Fig. 28-4, A). All of the skeletal components are present, all of the masticatory muscles are present, and function is within normal limits. There is a degree of asymmetric mandibular retrognathia, with a shift of the chin off of the facial midline. A limited degree of maxillary cant can usually be documented. Note: With Type I malformations, the condyle and the glenoid fossa are fully intact. There is no need to construct a new condyle or a new glenoid fossa.

A Type IIA mandible has a moderate degree of glenoid fossa and condyle–ascending ramus hypoplasia (see Fig. 28-4, B and C). By definition, the extent of hypoplasia results in the TMJ complex being located anteriorly and medially as compared with the normal side; however, joint function remains satisfactory. The masticatory muscles have a variable degree of hypoplasia. The mandible is retrognathic, the chin is shifted to the ipsilateral side, and an anterior open bite is frequently seen. A moderate maxillary cant is usually present. With a Type IIA malformation, despite significant hypoplasia, a decision to retain the TMJ complex (i.e., the condyle and the glenoid fossa) as part of the maxillomandibular reconstruction has been made.

The Type IIB mandible involves severe hypoplasia of the condyle–ascending ramus (see Fig. 28-4, D). The glenoid fossa has an anterior and medial location, but its placement is adequate for the construction of a neocondyle. The hypoplastic condyle, if it is present at all, is rudimentary and not substantial enough to seat into the glenoid fossa. There is not a consistent “posterior stop” to the mandible against the glenoid fossa. The mandible functions with rotation but not with a condylar component in the glenoid fossa, and there is little or no translational jaw movement. Vertical mouth opening is present (albeit reduced), with a shift of the chin to the ipsilateral side. The extent of mandibular dysmorphology, asymmetric retrognathia, and anterior open bite is marked. Variable but definite deficiencies of the masticatory muscles are present. There is usually significant hypoplasia of the ipsilateral maxilla, with obvious canting. By definition, with a Type IIB mandibular deficiency and deformity, the condylar remnant is too far displaced and rudimentary to be useful. Construction of a neocondyle–ascending ramus into the current acceptable glenoid fossa is required.

The Type III mandible is free-floating on the ipsilateral side, with no “posterior stop” of the lower jaw against the skull base on the affected side (see Fig. 28-4, E). The condyle and all or part of the ramus on the ipsilateral side are absent. The disc, the TMJ capsule, and the glenoid fossa are also not developed. Mandibular dysmorphology is severe and includes ipsilateral retrognathia and decreased posterior (ramus) facial vertical height. The masticatory muscles are severely hypoplastic, and the lateral pterygoid remnant is not attached to the mandibular structures. There is significant hypoplasia of the maxilla, with obvious canting. Occasionally, a tracheostomy is required shortly after birth to manage the airway compromise that results from a combination of factors, including (but generally not limited to) the degree of mandibular hypoplasia. By definition, with a Type III glenoid fossa–mandibular malformation, the eventual construction of both a neo–glenoid fossa and a neocondyle ascending ramus will be required to achieve successful maxillofacial reconstruction.

Staging of Skeletal Reconstruction: Timing and Techniques

The facial rehabilitation of the patient with HFM must address unique and specific components of the malformation that may include the following: 1) the zygomatic and orbital region; 2) the maxillomandibular regions; 3) the facial soft tissues; 4) the external ear; 5) the auditory canal; and 6) the middle-ear structures.*

Some clinicians have speculated that there is a reduced facial growth potential in patients with HFM which then leads to a progression of the primary malformation and secondary deformities of the maxillofacial skeleton. This assumption has led some to advocate early mandibular reconstruction to prevent progression. This author agrees with Rune and colleagues,225,226 Polley and colleagues,¹⁹⁴ Meazzini et al.^136A and Ongkosuwito and colleagues^161A that the observed facial asymmetry in patients with HFM is not progressive with ongoing growth (see the section earlier in this chapter about facial growth potential with HFM) (Figs. 28-5 through 28-7).^{203,209–212,233,234}

Consideration of First-Stage Mandibular Reconstruction during the Mixed Dentition