Craniofacialmicrosomia: Kathleyn A. Brandstetter,, Krishna G. Patel

C r a n i o f a c i a l M i c ro s o m i a
Kathleyn A. Brandstetter, MD*, Krishna G. Patel, MD, PhD
KEYWORDS
Craniofacial microsomia Hemifacial microsomia Oculoauriculovertebral syndrome
Distraction osteogenesis Costochondral grafting
KEY POINTS
There are several classification systems for craniofacial microsomia that group patients based on
their degree of asymmetry. The most recent and comprehensive of these is the OMENS PLUS
(Orbit, Mandible, Ear, Nerve, Soft tissue) system.
Treatment of craniofacial microsomia is based on the severity of the deformity.
Timing of surgical repair remains controversial.
Mandibular distraction osteogenesis is a well-accepted method of correction of mandibular asym-
metry but there is evidence of relapse if patients undergo distraction before completion of growth.
Treatment includes not only correction of skeletal deformities but also soft tissue deficits (by means
of free tissue flaps, fat grafting, and implants).
INTRODUCTION EPIDEMIOLOGY
Craniofacial microsomia (CFM) is a term used to CFM is the second most common craniofacial
describe a spectrum of craniofacial abnormalities birth defect after cleft lip and palate. It affects an
caused by abnormal development of the first and estimated 1 in 3600 to 5600 live births in the United
second pharyngeal arch derivatives. The term States each year. Literature reviews suggest that it
CFM is often used interchangeably with several is 50% more prevalent in boys (3:2 ratio). Ten
other terms, including otomandibular dysostosis, percent of cases are bilateral, and most unilateral
lateral facial dysplasia, malformation syndrome of cases occur on the right.2
the first and second arches, temporal oculoauricu-
lar dysplasia, and hemifacial microsomia (HFM). In CAUSE/PATHOGENESIS
addition, Goldenhar syndrome is considered a
variant of CFM, which also includes epibulbar der- The mechanism behind CFM is thought to be
moids and vertebral anomalies. It is thought that related to the development of the pharyngeal
the entities mentioned earlier represent several arch structures. The pharyngeal arches start to
different phenotypical presentations that exist form around the fourth week of embryologic devel-
within a continuum, and thus the term oculoauricu- opment and are composed of mesenchymal cells
lovertebral spectrum (OAVS) was proposed by that give rise to various facial structures (including
Cohen and colleagues1 in 1989 to encompass all skeletal, muscular, and neural elements). The
of these variants. Each of the variants includes morphogenesis of these structures depends on
some degree of developmental abnormality of continuous and reciprocal tissue-tissue interac-
the facial skeleton (mandible, maxilla, zygoma, tions, and any disruption of these interactions
can lead to developmental abnormalities.3,4 There
facialplastic.theclinics.com
and/or temporal bone), ear, and soft tissues.
Disclosures: Neither author has any conflicts of interest or disclosures.

Department of Otolaryngology Head and Neck Surgery, Medical University of South Carolina, 135 Rutledge
Avenue, MSC 550, Charleston, SC 29425, USA
* Corresponding author.
E-mail address: [email protected]
Facial Plast Surg Clin N Am 24 (2016) 495–515

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496 Brandstetter & Patel
are 2 leading theories to explain the pathogenesis gestational diabetes, exposure to teratogens
of CFM: such as thalidomide, vasoactive drug use, smok-
ing, and multiple gestation pregnancies cause
1. Vascular disruption of the stapedial artery dur- disruption of embryonic blood flow during fetal
ing development of the first and second development, leading to several structural
pharyngeal arch derivatives leads to hematoma congenital anomalies.42–44
formation and subsequent abnormal growth
and malformation of the mandible.5
2. Death, failure of development, or failure of PRESENTATION
migration of cells from the neural crest to the There are no established criteria for diagnosis of
pharyngeal arches, causing dysmorphology of CFM. However, several studies have indicated
the arches.6 that either mandibular or auricular defects are
mandatory for diagnosis. Cousley45 proposed in
his 1993 article the following minimum diagnostic
GENETICS
criteria:
The causes of CFM include both extrinsic and ge-
1. Ipsilateral mandibular and ear defects (external/
netic risk factors. Most documented cases are
middle)
sporadic with no relevant family history. However,
2. Asymmetrical mandibular or ear defects
there is growing evidence for a genetic predisposi-
(external/middle) in association with:
tion. Previously, a positive family history was
a. Two or more indirectly associated anoma-
documented in about 2% of patients who were
lies, or
within the OAVS spectrum. However, recent
b. A positive family history of HFM
studies have shown significantly larger numbers
of familial cases. It is also hypothesized that the re- There are varying degrees of severity within the
ported percentage of familial involvement is spectrum of CFM. Mandibular deficiency can
underestimated given the broad phenotypic spec- range from missing the condylar cartilage and
trum, with some family members having mild pre- disc to complete developmental failure of the
sentations that go undetected.7,8 In a study by ramus. The maxilla, temporal bone, and orbit can
Kaye and colleagues,9 44% of cases of CFM had also be affected as a result of primary malforma-
a positive family history of facial malformation, tion. However, CFM is not characterized by bony
with an overall recurrence rate of 2% to 3% in dysmorphism alone, because there is soft tissue,
first-degree relatives. Their data favored an auto- neural, and muscular involvement as well. Table 2
somal dominant mode of inheritance with incom- outlines the anomalies that are seen and their
plete penetrance rather than a recessive or incidence.
polygenetic mode of transmission.
Several chromosomal abnormalities have been CLASSIFICATION SYSTEMS
identified in patients with CFM (Table 1). Studies
reveal that the 22q11 locus may harbor genes The heterogeneity of phenotypic presentations in
important for regulation of craniofacial symmetry CFM has led to difficulty developing a reproducible
and first and second pharyngeal arch develop- classification system to distinguish between varying
ment, because craniofacial skeletal and soft tissue degrees of deformity and to help aid in surgical plan-
asymmetries have been observed in patients with ning.49 The first accepted classification was pro-
genomic imbalances on the 22q11 locus.40 The posed by Pruzansky50 in 1969, and focused on the
Crkl gene (in the 22q11 region) regulates signaling size and shape of the mandible and glenoid fossa.
events in developing pharyngeal arches, again Kaban and colleagues51,52 modified this classifica-
supporting its potential contribution to craniofacial tion system in 1988, proposing further stratification
dysmorphism.41 The OTX2 gene was also identi- of the type II mandible based on the relationship of
fied as a very likely causal gene in CFM. This the mandibular condyle and glenoid fossa (Fig. 1).
gene encodes a transcription factor that plays a Another classification system described in the liter-
critical role in craniofacial development and ante- ature is the SAT (skeletal malformations, auricular
rior brain morphogenesis. Zielinski and col- involvement, and soft tissue defects) system, pro-
leagues13 investigated the largest CFM pedigree posed by David and colleagues53 in 1987. Vento
to date and found that a duplication in chromo- and colleagues46 took this one step further, defining
some 14q22.3 (coding for OTX2) was present in the OMENS (Orbit, Mandible, Ear, Nerve, Soft tis-
all affected individuals. sue) classification system, which expanded the
Environmental factors are also thought to play a SAT system to include other affected structures:
causative role in CFM. It is hypothesized that orbital distortion, mandibular hypoplasia, ear
Craniofacial Microsomia 497
Table 1
Chromosomal abnormalities seen in CFM
Abnormality Gene Type Reference

22q11.2 Crkl Deletion Xu et al,10 2008; Digilio et al,11 2009; Tan et al,12 2011
14q22.3 OTX2 Zielinki et al,13 2014
3q29 Deletion Guida et al,14 2015
14q32 GCS Kelberman et al,15 2001
15q26.2–3 Huang et al,16 2010
1p22.2-p31.1 Deletion Callier et al,17 2008
12p13.33 Deletion Rooryck et al,7 2010; Adbelmoity et al,18 2011
Trisomy 22 Kobrynski et al,19 1993
14q23.1 Duplication Ballesta-Martinez et al,20 2013; Ou et al,21 2008
15q24 Deletion Brun et al,22 2012
5q13.2 Deletion Huang et al,16 2010
5p15.33-pter Deletion Descartes et al,23 2006; Josifova et al,24 2004; Ladekarl
et al,25 1968; Ala-Mello et al,26 2008
10p14-p15 Duplication Dabir et al,27 2006
14q31.1–3 Deletion Gimelli et al,28 2013
15q24.1 Deletion Brun et al,22 2012
Trisomy 18 Verloes et al,29 1991
Deletion 22qter Deletion Herman et al,30 1988
22q11.1–.21 Duplication Quintero-Rivera,31 2013; Torti et al,32 2013
X chromosome Garavelli et al,33 1999; Poonawalla et al,34 1980
aneuploidies
t(9;18) (p23;q12.2) Translocations Rooryck et al,7 2010
inv9(p11;q13) Inversion Stanojevic et al,35 2000
inv14(p11.2;q22.3) Inversion Northup et al,36 2010
Mosaicism trisomy 7 Mosaic Hodes et al,37 1981
Mosaicism trisomy 9 Mosaic de Ravel et al,38 2001; Wilson et al,39 1983
Mosaicism trisomy 22 Mosaic de Ravel et al,38 2001
8q13 Cousley et al,2 1997
deformities, nerve defects, and soft tissue defi- posteroanterior (PA) cephalogram is still the gold
ciencies. A modified version has since been pub- standard method for assessing facial asymmetry.
lished (OMENS PLUS), which is used when With these images, clinicians can measure maxillary
noncraniofacial structures are also involved.48 The and mandibular deviations from midline, differences
hope with these classification systems (outlined in in ramus height, and occlusal cant. These measures
Table 3) is that better differentiation of key pheno- are important in objectively assessing improvements
typical elements will lead to improved diagnosis, in asymmetry caused by surgical intervention.
treatment planning, prognostic predictions, data The major goals in treating CFM include im-
evaluation, and case correlation.4 provements in facial symmetry, functional jaw
movement, occlusion, and patient satisfaction.
TREATMENT OVERVIEW Kaban and colleagues54 outlined 4 main treatment
objectives:
Treatment of CFM poses a challenging issue
because there are both soft tissue and skeletal 1. Increase size of mandible and associated soft
deficiencies that need to be addressed. Before tissue
surgical intervention, computed tomography (CT) 2. Create temporomandibular joint (TMJ) if one is
with three-dimensional (3D) reconstruction is lacking
becoming an increasingly popular imaging modality 3. Foster vertical maxillary growth
to better delineate asymmetries. However, the 4. Obtain stable occlusion
Table 2
Clinical presentation of CFM
Percentage of
Site Patients (%)
Mandibular deficiency 89–100
Other Bony Anomalies
Maxillary hypoplasia —
Temporal bone deformity —
Orbit 15–43
Ear anomalies 65–99
Microtia/anotia 66–99
Preauricular skin tags 34–67
Conductive hearing loss 50–66
Ossicular chain defects —
Pinna abnormalities —
External auditory canal —
atresia
Soft tissue defects 17–95
Masticatory/facial muscle 85–95
hypoplasia
Parotid gland hypoplasia —
Deficiency of subcutaneous —
tissue
Transverse oral cleft 18–61
Cranial nerve involvement 10–45
Anomalies Outside Head and Neck
Vertebral/rib defects 16–60
Cardiac defects 4–33
Renal/genitourinary defects 4–15
Central nervous system 5–18
anomalies
Data from Refs.45–48
SURGICAL TIMING
Defining the timing of surgical intervention is chal-
lenging, because of the controversy as to whether
facial asymmetry in these patients progresses over Fig. 1. Examples of Pruzansky-Kaban type IIa (A), IIb
time or remains fixed. In reviewing the literature, (B), and III (C) deformities. (A, B) Both mandibular
there are 2 separate fields of thought: and auricular anomalies are present. (C) Multiple
additional anomalies, including orbital asymmetry
1. Clinicians who think that the asymmetry is pro- and lateral oral clefting.
gressive favor early surgical intervention.
2. Clinicians who think that the asymmetry is fixed
propose delayed intervention once the children
reach skeletal maturity. that mandibular skeletal asymmetry worsens
with time, because the affected side has little or
Note that both fields of thought agree on early no growth. They argue that early intervention al-
surgical intervention in children at risk for airway lows improved growth potential and functionality
compromise because of their mandibular of structures by minimizing secondary skeletal de-
deformity. formities caused by limited growth of adjacent
Those surgeons who support early correction structures. In addition, they think that early inter-
of asymmetry (before skeletal maturity) believe vention improves masticatory muscle hypoplasia,
Table 3
Grading systems for CFM
Pruzansky Classification of CFM (1969)50

Grade I Mandible with mild hypoplasia
Grade II Mandible with more severe hypoplasia in addition to malformation of common
bony landmarks
Grade III Mandible with complete effacement of common mandibular landmarks (absent
ramus, condyle, TMJ)
Pruzansky-Kaban Classification (1988)51
Grade I Mandible with mild hypoplasia
Grade II
IIa Mandibular ramus, condyle, and TMJ are present, normal in shape, but
hypoplastic
IIb Mandibular ramus is hypoplastic and markedly abnormal in form and location
(medial and anterior) without articulation with temporal bone
Grade III Mandible with complete effacement of common mandibular landmarks (absent
ramus, condyle, TMJ)
SAT Classification System (1987)53
Skeletal S1 Small mandible of normal shape
malformations S2 Mandible very different in size and shape than normal. Condyle, ramus,
and sigmoid notch identifiable but distorted
S3 Mandible severely malformed: ranges from poorly identifiable ramal
component to complete agenesis of ramus
S4 S3 mandible with orbital involvement: posterior recession of lateral and
posterior orbital rims
S5 S4 defect with orbital dystopia, hypoplasia and asymmetric
neurocranium, flat temporal fossa
Auricular A0 Normal
involvement A1 Small malformed auricle but all features are retained
A2 Rudimentary auricle with hook at cranial end corresponding with helix
A3 Malformed lobule and absent remainder of pinna
Soft tissue defects T1 Minimal contour defect without cranial nerve involvement
T2 Moderate defect
T3 Major defect, obvious facial scoliosis, severe hypoplasia of cranial nerves,
parotid, muscles of mastication, eye involvement; facial clefts
OMENS Classification (1991)46
Orbit (orbital O0 Normal orbital size and position
distortion) O1 Abnormal orbital size
O2 Abnormal orbital position
O3 Abnormal orbital size and position
Mandible M0 Normal mandible
(mandibular M1 Small mandible and glenoid fossa
hypoplasia) M2a Short mandibular ramus but good position of glenoid fossa
M2b Short mandibular ramus; TMJ is inferiorly, medially and anteriorly
displaced; condyle is hypoplastic
M3 Complete absence of mandibular ramus, glenoid fossa and TMJ
Ear (ear anomaly) E0 Normal ear
E1 Mild hypoplasia and cupping but all structures present
E2 Absence of external auditory canal with hypoplasia of concha
E3 Malpositioned lobule with absent auricle; lobular remnant inferiorly and
anteriorly displaced
(continued on next page)
Table 3
(continued )
Nerve (nerve N0 No facial nerve involvement

involvement) N1 Upper facial nerve involvement (temporal, zygomatic branches)
N2 Lower facial nerve involvement (buccal, mandibular, and cervical
branches)
N3 All branches of facial nerve involved
Soft tissue (soft S0 No obvious soft tissue or muscle deficiency
tissue deficiency) S1 Minimal subcutaneous/muscle deficiency
S2 Moderate subcutaneous/muscle deficiency
S3 Severe soft tissue deficiency caused by subcutaneous and muscular
hypoplasia
Abbreviation: TMJ, temporomandibular joint.
optimizes dental development, and affords reconstruct the mandible, whereas treatment of
improved patient aesthetic appearance and children with milder deformities tended to be
body image development.55 more variable. Many were not treated until adoles-
Those investigators in favor of waiting to correct cence or received functional orthodontic appli-
mandibular asymmetry think that the most favor- ances, whereas others underwent early
able aesthetic results come from reconstruction mandibular osteotomies to keep up with vertical
at an age closer to skeletal maturity (age 13–15 midfacial growth.60 Soft tissue deficiencies were
years in girls, 15–16 years in boys). They argue usually not addressed until after restoration of
that relapse of asymmetry occurs during growth bony symmetry.60
phases, leading to a need for multiple additional
procedures. They highlight technical reasons for MODERN APPROACH TO TREATMENT
delaying surgical reconstruction until the perma-
nent dentition phase, noting that procedures per- Regardless of timing of skeletal repair, the choice
formed later have decreased blood loss and of procedure is based on the severity of the defect
other surgical risk factors. Patient compliance and degree of deficit of mandibular bone stock. In
also improves in these cases compared with early the meta-analysis by Pluijmers and colleagues,61
distraction osteogenesis. patients with type I deformities were most often
Studies of the outcomes following early and late treated with MDO. However, elongation and rota-
skeletal correction of CFM vary greatly in terms of tion with osteotomy was also used to treat type I
results, and most of these studies are small and and IIa patients. Those with type IIa deformities
retrospective, consisting of level IV evidence. most commonly underwent MDO and those with
Several larger systematic reviews have been con- IIb deformities most commonly underwent recon-
ducted to address this issue, and these studies struction with grafts. Type III deformities were
concluded that there was a lack of evidence sup- most often treated with iliac or costochondral
porting early skeletal correction in these children. grafting to recreate the TMJ, sometimes followed
However, some institutions still support early by MDO.61
distraction. This article discusses the evolution of
GRAFTS
surgical treatment of CFM chronologically.
Gillies62 first described the use of cartilage and
HISTORY OF TREATMENT bone from the rib cage to address the hypoplastic
mandible in the 1920s. Along with providing
In the days before mandibular distraction osteo- adequate bony length, the cartilaginous portion
genesis (MDO), early mandibular reconstruction of the graft serves as a neocondyle. The most pop-
was achieved by mandibular osteotomy and ular graft material used is the costochondral carti-
autogenous grafting, most frequently using costo- laginous rib graft, followed by iliac crest,
chondral cartilaginous rib grafting.54,56–59 Dating interposed temporal bone, and fibula. Its popu-
back to the 1970s, the degree of the deformity in larity stems from the potential for growth along
CFM was used to guide treatment. Those children with its adaptability and workability. However,
with more severe defects (Pruzansky-Kaban types studies have suggested unpredictable growth pat-
IIb and III) underwent surgery prepubertally to terns and the potential for overgrowth on the
treated side. Grafting also has risks, including vector control of advancement,78 no donor site
infection, donor site morbidity, reankylosis, frac- morbidity, and an ability to lengthen the mandible
ture, and resorption.63 at a younger age.76,79
Follow-up studies of mandibular grafting
showed high rates of resorption of graft material
and recurrence of asymmetry.64 Thus, with the STABILITY OF DISTRACTION
advent of MDO, grafts became used mainly in
conjunction with distraction or in patients with Pru- In the decade following the advent of MDO,
zansky type IIb and III deformities requiring con- studies began to note the need for repeated
struction or reconstruction of the TMJ and distraction to maintain symmetry during
ramus. Occasionally, grafts were used in type IIa growth.80–83 Molina and colleagues84 published
patients as interposed bone to lengthen the one of the first of these studies in 1995, of 65 pa-
affected mandible. However, the normal side tients with CFM who were treated with early
outgrew the affected side after elongation in 50% MDO and followed for an average of 19 months
of patients.64 In addition, patients with costochon- postoperatively. Facial development on the unaf-
dral grafting before MDO tended to have higher fected side proceeded normally, whereas the
rates of postoperative complications (44%– distracted side showed delayed growth, leading
68%).64,65 to some return of asymmetry. Thus the investiga-
tors proposed overcorrection and second-stage
distraction.
DISTRACTION OSTEOGENESIS The concept of overcorrection has since been
Several cases of mandibular corpus distraction suggested in multiple additional studies as a
were reported in the literature during the first half method to combat the need for repeated distrac-
of the twentieth century,66–69 but the technique tion.51,54,82,83,85–87 However, overcorrection has
of MDO did not gain popularity until the early its downsides as well, including creating a dental
1990s when McCarthy’s group at New York Uni- crossbite on the contralateral side, leading to so-
versity began to perform the procedure.70 The called occlusal disasters.88,89 Overcorrection
technique was slowly adopted over the following also increases the abnormal form and position of
years but became widely accepted with the advent bone and soft tissues, creating a secondary chin
of bidirectional distraction (described by Klein and malformation, making future genioplasty more
Howaldt130 in 1995).60 The principal aims of MDO difficult.85,90 In addition, overcorrection did not
are to provide stable expansion of the mandible reduce the number of surgeries these children
with concurrent lengthening and expansion of sur- underwent.80–83
rounding muscle and soft tissue. Initially, mandib-
ular distraction devices were only external. These
devices offered excellent mechanical strength INCREASING SUPPORT FOR DELAYED
but had some complications, including unsightly SURGICAL INTERVENTION
pin site scars, pin site infections, and dislodge- Several systematic reviews have been conducted
ment of the device. These complications led sur- over the past decade of long-term stability of the
geons to design internal mandibular devices. distracted mandible in patients with CFM.60,61,91
These devices are inserted through either an oral The investigators all commented on the lack of
or external approach and provide excellent me- evidence-based data supporting early versus
chanical strength. The downsides include the delayed surgical intervention. All of the studies
need for removal at the end of the distraction consist of level IV evidence, and many of the
and bony overgrowth on the device, making studies are flawed in their design, making their
removal difficult.65,71 data questionable in terms of validity. Table 4 out-
Initial studies of MDO revealed some significant lines these studies. Conclusions were similar for all
advantages compared with costochondral graft- 3 systematic reviews:
ing. MDO increased the vertical length of the
mandible,72 produced greater bone stock,73 MDO performed before skeletal maturation
improved soft tissue asymmetry by encouraging leads to relapse of asymmetry, despite
hypertrophy of the muscles lying parallel to the overcorrection.
distraction vector,74–76 and had less relapse than The earlier the correction, the more likely the
costochondral cartilage grafting.76,77 In addition, procedure will need to be repeated.60
operative times were generally shorter; the compli- In addition, there was evidence suggesting
cations were fewer; the postoperative course was adverse effects of MDO on growth of the
simpler; and there was less blood loss, greater affected mandible.
502
Brandstetter & Patel

Table 4
Overview of literature
Publication Follow-up Level of

Author Study Design Therapy Period Long-term Outcomes Conclusions Evidence
Stability Following Surgery
Kaban et al,51 Retrospective case Elongation and 4y Stable occlusion with E&R, 50% IV
1988 series (n 5 17) rotation by of grafted mandibles
osteotomy vs outgrown by normal side
grafting
Kearns et al,55 Retrospective case Untreated >13 y Statistically significant Hemifacial microsomia is IV
2000 series (n 5 67) progression of asymmetry from progressive; early surgical
the deciduous to mixed intervention is warranted
dentition phase in all
measurements in group II
patients (mandible type IIB or
III)
Padwa et al,86 Retrospective case Grafting 5.5 y 16% of patients had significant Proposed overcorrection IV
1998 series (n 5 33) return of asymmetry as
determined by occlusal cant
Molina et al,84 Retrospective case Early MDO 19 mo Younger patients had faster Proposed overcorrection and IV
1995 series (n 5 65) growth on the unaffected side second-stage distraction
compared with the treated
mandible
Molina et al,88 Prospective case Early MDO 12 y Stable symmetry. In patients <5 y Stable symmetry IV
2004 series (n 5 4) old, secondary occlusal disaster
and need for reoperations seen
Hollier et al,81 Prospective case Early MDO 32.6 mo Growth of affected vertical ramus Proposed overcorrection IV
1999 series (n 5 8) slower than the unaffected side
in all patients
Grayson et al,92 Retrospective case Early MDO 1–6 y Increase in height over 5 y of Proposed overcorrection IV
1997 series (n 5 5) growth is greater on the side
that is not distracted
Baek et al,90 Retrospective case Early MDO 2.7 y Type I and IIa mandibles stable, IV
2005 series (n 5 19) type IIb and III mandibles with
relapse
Cavaliere Prospective case Early MDO 1–2 y Type III mandibles: improvement IV
et al,93 2002 series (n 5 2) in contour of affected side, full
range of jaw motion. No

mention of relapse at end of
follow-up
Altug-Atac Retrospective case Early MDO 6 mo Significant improvement in hard IV
et al,94 2008 series (n 5 11)
and soft tissue asymmetry, no

mention of relapse
Kulewicz et al,95 Prospective case Early MDO 3 mo to 1 y Stable results in lengthening and Proponent of early correction IV
2004 series (n 5 28) occlusion after 1 y. Coordinated
growth of maxillomandibular
complex
Shetye et al,96 Retrospective case Early MDO 5–10 y No alteration in growth pattern. Small amount of relapse but, by IV
2006 series (n 5 12) 1 y after MDO, 26.6% relapse in 1 y, asymmetry stabilized
ramus height, 40% relapse in
occlusal and bigonial plane
canting
Jansma et al,85 Retrospective case Early MDO 2.5 y Stable results until end of follow- No evidence of relapse following IV
2004 series (n 5 2) up MDO
Ortiz Retrospective case Iliac and 3.5–5 y Overcorrection used and, by end Proposed overcorrection IV
Monasterio series (n 5 6) costochondral of follow-up, slight decrease in
et al,97 1982 grafts overcorrection but no relapse
or increase in asymmetry
Trahar et al,98 Prospective case Early MDO 1–2 y Stable mandibular length Proponent of early correction IV
2003 series (n 5 6) without relapse
Gui et al,99 2011 Retrospective case MDO 1 graft 3y Greatly improved 3D facial IV
series (n 5 21) symmetry with minimal
relapse. 18 of 21 patients very
Craniofacial Microsomia
satisfied with results
Scolozzi et al,100 Retrospective case MDO 2.2 y Horizontal improvement in IV
2006 series (n 5 5) symmetry, stable
Satoh et al,101 Prospective case MDO 1.3–3.3 y Stable results with 2 of 10 IV
2002 series (n 5 10) patients showing slight occlusal
change
503
504

Table 4
(continued )

Huang et al,102 Prospective case MDO 1y Stable symmetry. More IV
1999 series (n 5 5) downward movement of chin
than forward movement
Munro et al,103 Retrospective case Grafting 1–9 y 16 of 18 with facial growth, 2 of IV
1989 series (n 5 22) 18 with overgrowth (and
relapse of asymmetry)
Vargervik Prospective case Grafting 5.2 y 11 of 14 stable with minimal IV
et al,57 1986 series (n 5 14) relapse/return of asymmetry
Ousterhout Prospective case Grafting 5.2 y 11 of 14 stable with minimal IV
et al,104 1987 series (n 5 14) relapse/return of asymmetry
Converse Retrospective case Grafting 3–12 y Residual asymmetry present but IV
et al,105 1973 series (n 5 12) stable (no relapse)
Relapse of Asymmetry
Mommaerts Meta-analysis (8 Early MDO NA Results revealed high percentage Despite initial correction, there is I
et al,60 2002 studies of overcorrection, repeated relapse of facial asymmetry.
included) osteodistraction procedures The earlier the correction, the
and soft tissue complications more likely that the procedure
will have to be repeated. MDO
may have possible adverse
effect on growth of affected
mandible. MDO does not lead
to lateral augmentation of soft
tissue
Nagy et al,91 Meta-analysis (13 Early MDO 3 m to 10 y 7 studies with stable results at No convincing evidence I
2009 studies end of follow-up (short-term or supporting effectiveness of
included) nonobjective evaluation), 6 early mandibular
studies with unstable results. osteodistraction
Type IIb, type III deformities
showed relapse with need for
reoperation
Pluijmers Meta-analysis (19 Early MDO, Most common intervention was Single-stage correction should be I
et al,61 2014 studies graft 1 MDO, bone grafting (CCG, rib, iliac). postponed until permanent
included) graft alone, Good results in short term but dentition phase or skeletal
E&R increased asymmetry over time maturity. Treatment of severely
with MDO and graft patients hypoplastic mandible should
(type II, III mandible). Most include multistage treatment
stable results in milder protocol
deformities
Kusnoto Retrospective case Early MDO 1.5 y Unoperated patients have fairly Mild relapse noted. Recommend IV
et al,106 1999 series (n 5 6) stable asymmetry over time. 3D evaluation for improved
Most favorable results found in surgical planning
body rather than ramus of
mandible. Slight decrease in
mandible length noted (w5%)
Marquez Case report Early MDO 2y Relapse of 87% of vertical Distraction osteogenesis does not IV
et al,107 2000 (n 5 1) distraction length, AP gain was accelerate growth and does not
stable. Soft tissue matrix predictably increase length of
decreased with MDO mandible
Meazinni Prospective case Early MDO 11 y, 5 y, 5.8 y Excellent postoperative results MDO is not stable over time IV
et al,108–110 series (n 5 14, but symmetry obtained was
2012, 2008, 17, 8) lost at completion of growth
2005 (nearly 100% loss of vertical
correction)
Batra et al,111 Retrospective case Early MDO 7y 30%–60% relapse in ramus IV
2006 series (n 5 3) height
Gursoy et al,112 Retrospective case Early MDO 5y No relapse in vertical or IV
2008 series (n 5 2) horizontal mandibular length.
Relapse of mandibular/skeletal
profile and form to
predistraction state
Polley et al,80 Retrospective case Unoperated 13 y No significant change in Skeletal mandibular asymmetry IV
1997 series (n 5 26) patients asymmetry over the 13 y of in HFM is not progressive in
growth. This finding was not nature. Growth on affected
influenced by grade and side of side parallels that of the
mandibular deformity nonaffected side
505
506

Table 4
(continued )

Rachmiel Retrospective case MDO 1y Some relapse in vertical IV
et al,113 1995 series (n 5 11) mandibular height noted
based on PA cephalograms
Huisinga- Prospective case Early MDO 1–3 y After 1 y, relapse in 50% of IV
Fischer series (n 5 8) patients. Relapse is progressive
et al,114 2003 3 y after MDO and all patients
showed relapse
Ko et al,115 2004 Retrospective case Early MDO 13 mo 30% relapse in ramus height, IV
series (n 5 10) 16% relapse in chin position.
Occlusal plane stable
Wan et al,116 Retrospective case MDO, graft alone, 13 y MDO patients with minimal Relapse seen more frequently IV
2011 series (n 5 47) graft 1 MDO relapse, 4 of 27 with increased with graft-only patients, most
asymmetry), 9 of 27 graft stable results in graft 1 MDO
patients with increased patients
asymmetry (and 2 of 27 with
overgrowth), 3 of 16
graft 1 MDO patients with
bone resorption and relapse
Santamaria Retrospective case Graft alone 3.8 y 6 of 8 graft patients with partial IV
et al,117 2008 series (n 5 8) (fibular free improvement in occlusion, 2 of
flap), 8 with total improvement; 3 of
graft 1 MDO 8 patients with increased
asymmetry long term; 2 of 2
graft 1 MDO patients with
partial improvement, no
mention of relapse
Chow et al,118 Retrospective case MDO 7y Outgrowth of normal side after IV
2008 series (n 5 4) 2 y. Relapse of asymmetry
noted
Cerajewska Prospective case Grafting 4y Bilateral growth of ramus, IV
et al,119 2002 series (n 5 14) minimal relapse of mandibular
body length
Hay et al,120,121 Prospective case Grafting 3.5 y Bilateral growth of ramus, IV

2000, 2000 series (n 5 15) minimal relapse of mandibular
body length
Singh et al,122 Prospective case Grafting 3y Bilateral growth of ramus, IV
1999 series (n 5 14) minimal relapse of mandibular
body length
Padwa et al,86 Retrospective case Grafting 5y 42% successful (<5 occlusal IV
1998 series (n 5 33) cant), 42% acceptable (5 –8 ),
16% unsuccessful (>8 ); 50% of
grafted mandibles outgrown
by normal side
Mulliken Retrospective case Grafting 4.5 y 42% successful (<5 occlusal IV
et al,123 1989 series (n 5 8) cant), 42% acceptable (5 –8 ),
16% unsuccessful (>8 ); 50% of
grafted mandibles outgrown
by normal side
Abbreviations: AP, anteroposterior; CCG, costocartilaginous rib graft; E&R, elongation and rotation; NA, not available; PA, posteroanterior.
507
With respect to soft tissue deficits, they concluded TEMPOROMANDIBULAR JOINT

that soft tissue management is best performed RECONSTRUCTION
separately from skeletal surgery.60
Based on the results of their analysis, Nagy and In type III cases in which patients have unstable
colleagues91 proposed their own treatment time- occlusion, a TMJ has to be created in addition to
line for patients with CFM, emphasizing postpone- lengthening the affected mandibular ramus. Even
ment of definitive reconstruction of type I, IIa, and with multidirectional distraction osteogenesis, it
IIb deformities until the permanent dentition phase is impossible to induce formation of the joint at
(Box 1). Several additional investigators have pro- the right location given the medially displaced, hy-
posed treatment timelines, including Cousley and poplastic remnant structures. Total joint recon-
Calvert,2 who stratified their protocol based on pa- struction (often combined with orbitozygomatic
tient age (Box 2). reconstruction) is often performed during the
The most recent meta-analysis of long-term mixed dentition phase. Surgical options include
stability following treatment of CFM was pub- costochondral grafting, cranial bone grafts, total
lished in 2014 by Pluijmers and colleagues.61 It TMJ prostheses, and/or microvascular free tissue
assessed 285 patients who underwent surgical transfers. Costochondral grafting has been the
treatment of mandibular asymmetry in HFM, gold standard technique for most type III defor-
including MDO, elongation and rotation by osteot- mities and studies have found that mandibular
omy, grafting, and the combination of grafting symmetry and occlusion improved considerably
plus MDO. Their results are summarized in with this procedure. However, studies have again
Table 5. They concluded that more stable results shown that the later it is performed the more stable
were seen in patients with milder deformities the result. Regardless of timing of initial TMJ
(types I–IIa) and the best results for both mild reconstruction, the final facial rotation surgery is
and severe cases were seen with the combination done in the permanent dentition phase.60 Some in-
of grafting followed by MDO. Based on their anal- vestigators, such as Polley and Figueroa,80 prefer
ysis, Pluijmers and colleagues61 recommended interim distraction in type III mandibles to help
postponing single-stage skeletal correction until improve (but not correct) facial symmetry before
the permanent dentition phase or completion of reconstruction of the TMJ. However, they do not
growth.61 reconstruct the lateral temporozygomatic defi-
ciency and condylar abutment at that time.
SOFT TISSUE CORRECTION

Box 1
Nagy and colleagues’91 proposed treatment The soft tissue deficits in patients with CFM are
outline multidimensional, with varying degrees of defi-
ciency noted in skin, subcutaneous tissue, mus-
Type I, IIa patients
cles of mastication, and the parotid gland.
Presurgical orthodontics Supporters of MDO initially claimed that the sur-
Standard 3D orthognathic correction during rounding soft tissues increased in volume during
permanent dentition phase lengthening secondary to muscle hypertro-
phy.80,83,88,89,124–126 However, the issue remains
Type IIb
controversial because multiple other studies
Standard 3D orthognathic advancement with have shown a decrease in soft tissue volume in
positional correction during permanent denti- response to skeletal enlargement by MDO.54,107
tion phase In cases in which the soft tissue correction is war-
If bone stock limited, extra volume can be ob- ranted, experts support proceeding with skeletal
tained with unidirectional corpus distraction realignment before correction of soft tissue deficits
1 year before facial rotational surgery or with to avoid the need of additional soft tissue proce-
interpositional bone grafting dures in the future. Options for surgical correction
Type III include microvascular free tissue transfer
Reconstruction of TMJ during mixed dentition
(including fasciocutaneous and osseocutaneous
phase options, with the parascapular flap being one of
the most popular), serial autologous fat grafting,
Data from Nagy K, Kuijpers-Jagtman AM, Mommaerts and implants.81,127
MY. No evidence for long-term effectiveness of early
Tanna and colleagues127 compared serial autol-
osteodistraction in hemifacial microsomia. Plast Re-
constr Surg 2009;124(6):2061–71. ogous fat grafting with microvascular free flap and
concluded that serial fat grafting was a useful
Box 2
Cousley and Calvert’s2 timeline of treatment of CFM
I. Infancy
Correction of soft tissue defects such as preauricular tags, cleft lip/palate, and gross macrostomia
Nerve graft repair of facial palsy
Hearing augmentation (hearing aids)
Osteotomies to correct clinically significant orbital dystopia and plagiocephaly
Elongation of mandible by bone distraction or costochondral grafting in cases with severe skeletal
defects leading to respiratory or feeding problems
II. Mixed dentition (approximately 6–12 years of age)
Reconstruction of malformed auricles using either autogenous rib cartilage grafts or osseointe-
grated implants (for prosthetic ears)
Middle ear reconstruction (predominantly bilateral cases)
Composite nerve and muscle grafts repair of facial palsy
Promotion of mandibular and maxillary growth, and masticatory function using 1 or more of the
following techniques:
Orthodontic functional appliances
Costochondral grafts to reconstruct the condyle-ramus unit and TMJ
Mandibular distraction or interpositional rib grafts
III. Adolescence and adulthood
Final orthodontic and orthognathic surgical correction of facial skeleton and occlusion, including
adjunctive use of bone recontouring, onlay bone graft techniques, and vascularized bone grafts
Soft tissue augmentation, including vascularized free tissue transfer, to redress any significant
asymmetry persisting after bony reconstruction
Definitive correction of auricular morphology, position, and secondary defects
Data from Cousley RR, Calvert ML. Current concepts in the understanding and management of hemifacial microsomia.
British J Plast Surg 1997;50(7):536–51.
alternative to the microvascular flap after skeletal MI) can be used to augment areas of soft tissue
reconstruction. The mean number of procedures deficiency. These synthetic implants can be pre-
was less for the free-flap group versus the fat- formed or custom designed from 3D CT image
grafting group, but the combined surgical time guidance. However, there are limited data for the
was much greater for the free-flap group. The vol- outcomes of such implants.
ume of soft tissue implanted and the symmetry rat-
ing were 20% to 25% higher in microvascular CORRECTION OF EAR ANOMALIES
group than the fat-grafting group, but the compli-
cation rate was also higher for this group. No The ear anomalies associated with CFM can
statistically significant difference in patient or involve the outer ear, external auditory canal, and
physician satisfaction was noted.127 Thus, either middle ear structures and range from mild hypo-
option is reasonable, and the investigators recom- plasia to anotia. The surgical treatment of these
mended basing decisions on whether the patient anomalies parallels treatment of isolated ear de-
will be returning to the operating room for other formities. Patients with mild hypoplasia and
procedures during childhood, making it possible cupping can be treated with simple reshaping of
to coordinate serial fat grafting during these times. the existing cartilage in many cases. As the defor-
Several studies have investigated the use of im- mity worsens and the bony deficiency becomes
plants, such as high-density porous polyethylene, more severe, treatment is more extensive and
to augment the hypoplastic mandible in achieving a good aesthetic outcome becomes
HFM.128,129 In addition, alloplastic material such more challenging. Various materials have been
as Medpor (Stryker Craniomaxillofacial, Portage, used for ear reconstruction, each with its risks
Table 5
Pluijmers and colleagues’61 long-term outcomes results based on treatment type and mandibular
classification
Pruzansky-Kaban
Treatment Type Classification Long-term Results
MDO (n 5 104) Type I (n 5 14) Minimal relapse
Type I and IIa (n 5 39) Slight increase in asymmetry in first year, 43% of
patients with relapse at 5 y
Type II (n 5 4) Slight decrease in mandibular length
Type IIa (n 5 24) 46% of patients with relapse of asymmetry
Type IIb (n 5 12) >50% of patients with relapse (exact numbers
not included)
Type III (n 5 11) >50% of patients with relapse (exact numbers
not included)
Elongation and rotation Type I (n 5 6) Stable results
(n 5 6) Type IIa (n 5 1) Stable results, mild chin point deviation
Iliac/rib graft (n 5 19) Type IIa (n 5 19) Minimal relapse
Fibular free flap (n 5 8) Type IIb (n 5 1) Minimal relapse
Type III (n 5 7) Increased asymmetry
Costochondral graft Type IIb (n 5 19) 75% of patients with relapse of asymmetry
(n 5 44) Type III (n 5 25)
Mandibular cortex Type I (n 5 11) Minimal relapse
graft 1 MDO (n 5 21) Type II (n 5 4) Minimal relapse
Type III (n 5 6) Minimal relapse
Fibular free flap 1 MDO Type III (n 5 2) No relapse
(n 5 2)
Costochondral graft 1 Type III (n 5 16) 12.5% of patients with relapse
MDO (n 5 16)
Data from Pluijmers BI, Caron CJ, Dunaway DJ, et al. Mandibular reconstruction in the growing patient with unilateral
craniofacial microsomia: a systematic review. Int J Oral Maxillofac Surg 2014;43(3):286–95.
and benefits. Autologous reconstruction is multi- limited mouth opening, and open-bite deformity,
staged and generally involves the use of costal as well as the tendency for external fixation pins
cartilage grafts to recreate the auricular frame- to loosen.64,81,91,130–132 With MDO in type IIb and
work. Several groups have also studied the use III patients, there is risk for posterosuperior move-
of alloplastic materials such as porous polyeth- ment of the proximal jaw segment (small and
ylene, which would avoid donor site morbidity; easier to move) causing uncontrolled displace-
allow reconstruction in younger, smaller patients; ment and relapse of facial asymmetry after
and typically provide stable rigidity. However, removal of the device.133,134
use of these materials is still controversial. Further-
more, the details of these procedures are beyond
SUMMARY
the scope of this article.113
CFM is characterized by anomalies of the first
SURGICAL COMPLICATIONS and second pharyngeal arch structures and in-
cludes a wide spectrum of phenotypes ranging
As with any surgical procedures, the techniques in severity. Treatment of these patients de-
discussed earlier have risks. Grafting procedures pends on the degree of deformity of the facial
(most notably mandibular grafting) can be unpre- framework. Classification systems have
dictable because of the risk for undesirable emerged over the years to better stratify these
resorption (described earlier), leading to patients and develop a standardized treatment
decreased volume and strength of the recon- algorithm based on patient class. There are still
structed area. These patients also experience debates regarding the timing of surgical correc-
morbidity at the donor site. In terms of MDO, risks tion for these patients, because some individ-
include pin-track infections, tooth germ injury, uals support early intervention and others
pain, hypertrophic facial scars, device fracture, encourage providers to wait until completion
of growth to surgically correct their bony asym- abnormalities. Am J Med Genet A 2011;
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Craniofacialmicrosomia: Kathleyn A. Brandstetter,, Krishna G. Patel

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Craniofacialmicrosomia: Kathleyn A. Brandstetter,, Krishna G. Patel

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C r a n i o f a c i a l M i c ro s o m i a

Kathleyn A. Brandstetter, MD*, Krishna G. Patel, MD, PhD

and/or temporal bone), ear, and soft tissues.

Disclosures: Neither author has any conflicts of interest or disclosures.

Facial Plast Surg Clin N Am 24 (2016) 495–515

Abnormality Gene Type Reference

Pruzansky Classification of CFM (1969)50

Nerve (nerve N0 No facial nerve involvement

Abbreviation: TMJ, temporomandibular joint.

Brandstetter & Patel

Publication Follow-up Level of

range of jaw motion. No

and soft tissue asymmetry, no

Brandstetter & Patel

Publication Follow-up Level of

Brandstetter & Patel

Publication Follow-up Level of

Hay et al,120,121 Prospective case Grafting 3.5 y Bilateral growth of ramus, IV

With respect to soft tissue deficits, they concluded TEMPOROMANDIBULAR JOINT

SOFT TISSUE CORRECTION

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