Hemifacial microsomia: treatment alternatives—a systematic review of literature

Background

Hemifacial microsomia (HFM) is a craniofacial syndrome, second in prevalence after cleft/lip and palate, affecting one in 3000–5600 newborn subjects. It is almost always unilateral, as indicated by the name, more prevalent in the right side (70–90% cases), and in male than female adolescents [1, 2, 3]. HFM is considered to be a congenital syndrome, that is, genetic but not inherited.

Description

HFM is a syndrome that causes asymmetrical anomalies in structures derived from the first/second pharyngeal arches: mandible, mandibular condyle, articular cavity, maxillary bone, orbit, auditory canal, ear, soft tissues and muscles innerved by trigeminal and facial nerves [4].

The severity of the disorder is highly variable, depending on the number of structures directly or indirectly involved and the penetrance of the syndrome. The facial asymmetry is due to underdevelopment of one facial side and transversal changes in the mandibular position related to reduced development of temporomandibular joint (TMJ) components and mandibular ramus [4]. Structures adjacent to bony components which present vertical changes in the affected side cause maxillary, occlusal and commissural canting. The lack of secondary development of the maxillary, zygomatic and malar bone affects the adjacent soft tissues as well [5].

When facial microsomia is bilateral, the consequent severe mandibular retrognathism affects masticatory, swallowing and respiratory functional processes [6, 7]. Depending on the severity of the syndrome, it becomes evident immediately after childbirth and the sequelae are progressive if adequate treatment is not initiated [8].

HFM was first described by Carl F. von Arlt in 1881, but it was also known as Goldenhar syndrome because a variant was described by the ophthalmologist Maurice Goldenhar in 1952, although some authors have not considered both terms to be equivalent until current evidence proved that this was a variant of HFM [9]. It is also known as otomandibular dysostosis, oculo-auriculo-vertebral dysplasia, oral-mandibular syndrome and unilateral hemi-mandibular hypoplasia [10].

Etiopathogenesis

The etiopathogenesis of HFM is multifactorial and is related to genetic and environmental factors. Family antecedents are reported in just a few cases [9]; however, different mutations and genes are involved in the etiopathogenesis of HFM. Most investigators suggest that the pathogenesis of this syndrome is the altered migration of neural crest cells during embryonal development [11], abnormal vascularization (stapedial artery hemorrhage) during the fourth week of pregnancy [2], and external factors such as the use of vasoactive medication, nicotine and cocaine exposure, thalidomide and hormonal therapy [12]. A higher risk has been reported in mothers with diabetes [13], hypothyroidism, rubeola, celiac disease, multiple pregnancy, vaginal bleeding during pregnancy or premature delivery [9].

Classifications

Pruzansky classified HFM in three grades: Grade I is characterized by minimal mandibular hypoplasia, with normal structures; Grade II is defined by a small condyle, ramus and sigmoid notch, and variable abnormal shape; Grade III is characterized by the absence of a mandibular ramus, including TMJ [14]. This classification was modified by Kaban et al. [15] who divided Grade II into two types: Type IIA and Type IIB. In HFM Grade I, it is fully accepted that all the TMJ components are present and have normal shape, but presenting different grades of hypoplasia. The glenoid cavity has a normal shape and the masticatory muscles are normally developed. In HFM Grade II, the TMJ is functional but the condylar head and glenoid cavity present an abnormal shape. In the Type IIA subcategory, both show hypoplasia and inadequate position allowing a mandibular functional movement, while in Type IIB the mandibular ramus shows hypoplasia and shape and location are abnormal causing TMJ malfunction. In HFM Grade III, the mandibular ramus, condyle and TMJ are absent and the masticatory muscles are not inserted into the mandible [15].

Vento et al. [16] established the OMENS (orbit, mandible, ear, nerve, soft-tissue) classification that has been complemented by a series of amendments to evaluate the orbit asymmetry, external ear deformation, nerve compromise and soft tissue deficiencies that might be present in the HFM spectrum of clinical presentations.

Differential diagnosis

The differential diagnosis of HFM includes pseudo-HFM or hemi-mandibular hypoplasia with condylar coronoid collapse (HHCCC), a condition without any soft tissue defects [17]. With HHCCC, the radiographic image shows collapse of the condyle and the coronoid apophysis, a condition that was not included in the classifications of Pruzansky and Kaban [14, 15]. It usually shows ramus, condyle and glenoid cavity hypoplasia [17]. In both entities, chin deviation toward the hypoplastic side is common. The temporal fossa (glenoid cavity) is always present in HHCCC, but not in HFM [2].

It is also important for a differential diagnosis to include a genetic analysis to rule out other syndromes such as Treacher-Collins, Miller-Dierker, Parry Romberg, CHARGE, Townes- Brocks, Branquio-oto renal, among other facial alterations [4]. The HFM diagnosis is sufficiently based on a detailed physical examination, clinical records and the analysis of 2D and 3D craniofacial images, but it should be complemented by molecular analysis interpreted by a geneticist to understand its characteristics and any familiar components [18].

Treatment

Regarding the treatment options, the literature reports different modalities depending on factors such as the patient’s age, severity of symptoms and the specialist who initiates the treatment [10, 22, 23].

The clinical presentation of HFM includes dental and occlusal findings that require collaboration between orthodontists, dentofacial orthopedists, and maxillofacial surgeons.

Multidisciplinary team management is recommended due to the potential for ocular, auditive, neurologic, cervical, gastro-intestinal, kidney and cardiac compromise [19, 20, 21]. The skeleto-dento-facial treatment objectives are:

—To increase the mandibular size and soft tissues associated with the affected side

—To provide a functional simulation of the TMJ when this structure is absent

—To correct secondary deformities in the maxilla

—To improve dental position and smile arch

—To correct dental canting

—To establish a functional occlusion

—To increase the range of buccal opening when it is limited

—To improve facial and dental esthetics

The treatment of HFM includes surgical procedures such as osteogenic distraction [24] and orthognathic surgery to correct the asymmetric growth of bone structures [25, 26]. Orthopedic interventions use multiple functional appliances, mainly the asymmetrical (AFA) [27] or hybrids [28], which use unilateral bite blocks to favor the vertical development of the affected side and also asymmetrical maxillary expansion [24]. As for orthodontic treatments, it is common to use intermaxillary elastics and temporary anchorage devices (TADs) [29, 30] to establish differential forces.

The combined treatments are variable according to the affected structures, the severity of impairments, the age of the patient, and the expertise and preferences of the clinical team. Currently, there are no established protocols for treating HFM.

Relevance of the present systematic review of literature

HFM is a complex deformity disorder that poses a challenge to clinicians. The treatment is almost always institutional and intra-hospital and must be initiated from childbirth, so it is not commonly seen in the independent professional practice. Mild cases can be misdiagnosed from isolated symptoms, which highlights the importance of knowing about the condition, its variability and the treatment alternatives. A systematic review of this topic provides a complete and comprehensive view of the treatment approaches, including orthodontics, orthopedic and surgical common options to manage HFM and the related sequelae.

Eligibility of articles

Study designs: Randomized controlled clinical trials, observational retrospective and prospective studies, case series, case-control and case reports.

Participants: The patients included in the study had an HFM diagnosis and were young enough to still have a potential for growth and development including residual growth (less than 22 years). There was no distinction for gender, ethnicity nor racial identity.

Interventions: The studies must describe orthodontic/orthopedic treatments with or without surgical procedures to correct HM and be free of treatment-related sequelae.

Outcome measurements: Type of treatment provided efficacy of the therapy in meeting the treatment objectives (maxillary canting correction, asymmetry correction, malocclusion and mandibular growth correction in the affected side).

Search methods

Sources of information: The data bases consulted were Scopus, Embase, Ovid, Cochrane Library and PubMed.

Electronic search: The time Interval was 1970—November 2021. No language or date of publication restrictions was applicable. The search equation used was:

((((((((((((((((((((Goldenhar (Title/Abstract)) OR (Oculoauriculovertebral Dysplasia (Title/Abstract))) OR (Dysplasia, Oculoauriculovertebral (Title/Abstract))) OR (Oculoauriculovertebral Dysplasias (Title/Abstract))) OR (Oculoauriculovertebral Spectrum (Title/Abstract))) OR (Oculoauriculovertebral Syndrome (Title/Abstract))) OR (Craniofacial Microsomia (Title/Abstract))) OR (Microsomia, Craniofacial (Title/Abstract))) OR (Facioauriculovertebral Dysplasia (Title/Abstract))) OR (Dysplasia, Facioauriculovertebral (Title/Abstract))) OR (Goldenhar Gorlin Syndrome (Title/Abstract))) OR (Goldenhar Disease (Title/Abstract))) OR (Lateral Facial Dysplasia (Title/Abstract))) OR (Oral Mandibular Auricular Syndrome (Title/Abstract))) OR (Otomandibular Dysostosis (Title/Abstract)))) OR (First and Second Branchial Arch Syndrome (Title/Abstract))) OR (Facioauriculovertebral Sequence (Title/Abstract))) OR (Hemifacial Microsomia (Title/Abstract))) OR (Craniofacial Microsomias (Title/Abstract))) AND ((((orthognathic (Title/Abstract)) OR (orthopedic (Title/Abstract))) OR (orthodontic (Title/Abstract))) OR (dentistry (Title/Abstract)))

Data extraction and analysis

Selection of articles: The first selection was performed by reading abstracts and/or summaries. Data extraction and risk of bias were performed independently by two investigators (DA, DR). In the event of a disagreement, a consensus for selection of the article was obtained. Both investigators filled a table for extraction and analysis of the variables to be considered.

The data list included:

Type of treatment

$◯$ Orthodontics

$◯$ Maxillary Orthopedics

$◯$ Orthognathic, maxillofacial surgery

Variables in the treatment used

$◯$ Fixed appliances such as brackets

$◯$ Intermaxillary elastics

$◯$ Temporary anchorage devices (TADs)

$◯$ Auxiliary treatment (including maxillary expansion)

$◯$ Functional Orthopedics

$◯$ Extraoral Orthopedics

$◯$ Orthognathic maxillofacial surgery

$◯$ Osteogenic distraction surgery

$◯$ Complementary therapies

Outcome variables

$◯$ Correction of occlusal plane canting

$◯$ Correction of malocclusion

$◯$ Condylar and mandibular growth of the affected side

$◯$ Asymmetry Correction

$◯$ Treatment time

$◯$ Follow up time

Population characteristics included in the study

$◯$ Age

$◯$ HM Classification

$◯$ Affected side

$◯$ Number of patients of each gender

Risk of bias evaluation

(1) For case reports and case series: the instrument used by Murad et al.[32]

(2) For observational cohort and case-control: New Castle Ottawa

(3) For randomized controlled studies: Cochrane ReMan

Risk of bias assessment

The Murad et al. [32] scale for analyzing bias in case reports and case series was modified by assigning a numerical value to Questions 1–6, classifying high risk bias as 1–2, moderate risk as 3–4, and low risk as 5–6. Four investigators (D.L, D.R, D.A and C.M: two of them are experts in systematic reviews) performed the risk of bias analysis and checked previous verification of the inter-observer agreement in the evaluations (Table 4).

In the case report and case series studies, four articles presented moderate risk of bias while the other one presented a low risk of bias relative to the description of adverse effects, differential diagnosis and long-term follow up (Table 4).

The two case-control studies evaluated for risk of bias using the Newcastle Ottawa instrument that evaluates selection criteria, comparability, and exposure presented low risk of bias (Table 4).

The RCCT study that was analyzed with the Cochrane instrument (Program Review Manager 5.4.1) qualified as having a low risk of bias in all aspects (Supplementary Fig. 1).