§What is HFM ?
§Take Home Message
• Pharyngeal arches are bulges forming on the lateral surface
of the embryo
• First evident after weeks 3-4 of human development (Graham
4(Santagati, F., Rijli, F. M., 2003)
First and second branchial arch syndromes manifest as
combined tissue deficiencies and hypoplasias of the face,
external ear, middle ear and maxillary and mandibular arches.
5(Santagati, F., Rijli, F. M., 2003)
• Hemifacial microsomia (HFM) is defined as a condition that
involves an absence or underdevelopment of structures that arise
from the first and second pharyngeal arches
• The disorder varies from mild to severe, and occurs on one side in
• Goldenhar syndrome is considered to be a variant of this
complex, characterized by vertebral anomalies and epibulbar
• The term oculoauriculo-vertebral spectrum (OAVS) is employed
to group these syndromes, which are extremely complex and
7Gemilli et al. 2013Birgfeld and Heike 2012
• The birth prevalence was estimated to be 1/5600
• Although most cases are sporadic and a few families consistent
with autosomal recessive inheritance have been reported, other
families clearly support autosomal dominant inheritance
• Infant boys are affected more often than infant girls (3 : 2)
• The right side of the face and/ or body being more commonly
and severely affected than the left side
su et al. 2007Passos Bueno et al. 2009 www.OMIM.org
• Both genetic and environmental causes are implied in the
pathogenesis of the syndrome
• Vascular abnormalities
• Hypoxia attributed to living at high altitude, maternal diabetes
and teratogens including thalidomide and retinoic acid
• Use of vasoactive medications and smoking are also risk
• The exact etiology of HFM has not yet been determined, but
appears to involve a disruption in the development of the first
and second pharyngeal arches during the first 6 weeks of
Birgfeld and Heike, 2012Kelberman et al. 2001Haratz et al. 2011
The principal features include :
1. Facial asymmetry
2. Teeth abnormalities
3. Masticatory muscles affected
4. Microtia often associated with preauricular skin tags or pits,
and conductive hearing loss.
Gemilli et al. 2013
Mishra et al. 2013
- Orbital asymmetry or upper eyelid colomboma
- Facial nerve supply might be affected.
- Soft tissue might be affected by defeciency of masculature or
lack of subcutaneous fat.
- Other craniofacial features, including macrostomia,
micrognathia, and cleft lip with or without cleft palate, can be
- There may be ocular dermoids and vertebral anomalies these
cases tend to be given the diagnosis of Goldenhar syndrome.
- Cardiac, renal, skeletal, and central nervous system defects
are more rarely observed
Gemilli et al. 2013 13
Mishra et al. 2013
Asymmetry in the mandibular
growth causing deviation to the
affected side and that’s what is
causing the facial asymmetry
- Malocclusions --proportional to the skeletal discrepancies.
- Typically, the side affected: crowding, inclination of the anterior
teeth toward the affected side and a unilateral crossbite.
- Tooth size smaller on the affected side
- Tooth development may be delayed on the affected side. Only if
asked!!!(Pathogenisis might be related to delay in the development
of the dental lamina Farias and Vargervik, 1988)
- 25 % prevalence of congenitally missing teeth. Dental agenesis
correlated to the severity skeletal malformation .
- (Enamel hypoplasia has been documented in the primary incisors
on the affected side, suggesting that the primary dental enamel
may serve as a developmental marker for the timing of the events
leading to the condition)
- (For normal odontogenesis, the presence and interaction of normal
neural crest ectoderm and of neural-crest-derived mesenchymal
cells are required.
- Disturbances in the odontogenic process can produce abnormal or
incomplete dental development)
Maruko et al. 2000
The teeth most commonly missing is the mandibular 2nd premolar, (followed by the
maxillary second molar, mandibular second molar, mandibular lateral incisor,
maxillary second premolar, and maxillary lateral incisor).
Farias and Vargervik in 1988 stated that the most frequently missing teeth is the
mandibular 3rd molar and 2nd premolar
- The difference in size between the affected and contralateral side was higher for the
- In subjects with type IV anomaly, significant differences were found for the
permanent mandibular first molar.
- In patients with type V anomaly, significant differences were found for the permanent
mandibular canine and mandibular first molar.
- six subjects (15%) had a four-cusp mandibular first molar on the affected side and a
five-cusp mandibular first molar on the contralateral side.
(Morphological abnormalities of the mandibular first molar were found in subjects with
HFM type III (one patient), type IV (two patients) and type V (three patients).
Heude et al. 2011 21
- A,B: right (unaffected side) and left
(affected side) view of a skull 3D
- C: Ct scan section showing the
- D,E: right and left view of masticatory
muscle 3D reconstruction. absence of
masseter muscle (in red) on the
affected side and the strong reduction of
the temporal muscle (in blue). The
pterygoid muscle global volume is
reduced by 31%.
1. Pruzansky Classification System
2. Kaban’s modification of the Pruzansky classification system
3. Tenconi and Hall Classification
4. Munro and Lauritzen (anatomical surgical classification)
Rodgers et al. 1991 24
5. Rollnick and associates classification (According to phenotype)
6. SAT staging system proposed by David et al.
Birgfeld and Heike,
Rodgers et al. 1991
• Surgical treatment requires a coordinated team approach
involving multiple specialties, which can include plastic
surgery, craniofacial surgery, orthognathic surgery, and
• A wide variety of surgical options exist, and individual
treatment plans should be based on the patient’s needs
Birgfeld and Heike, 2012 28
• Procedures for the eye and orbit in CFM typically involve either
bony or soft tissue surgery
• Infants require treatment of epibulbar dermoids if the visual axis is
disrupted. Eyelid colobomas may require repair to protect the
cornea and prevent exposure keratitis and blindness
• Orbital asymmetry is corrected only if severe and typically is
postponed until the orbital growth is complete at around age 3 or 4
• Orbital repositioning is performed by a circumferential box
osteotomy performed through an intracranial approach
Birgfeld and Heike, 2012 29
1. Type I
2. Type IIA
3. Type IIB
4. Type III
Birgfeld and Heike, 2012
• When the physician identifies facial nerve palsy, she must first
determine whether the patient can protect and lubricate his
cornea. If not, eye drops, lubricant, or a surgical procedure
should be considered
• A facial reanimation procedure should be considered for a
patient who cannot move his or her mouth due to deficiencies of
the buccal and marginal mandibular branches.
Birgfeld and Heike, 2012
1. Free Flap: An adipofascial free flap is the best way to provide
a large amount of soft tissue in a single surgical procedure
for patients with severe deficiencies
2. Dermal Fat Graft: Can provide adequate bulk in moderate
and mild deformities, but are prone to some degree of
resorption and patients may require additional
3. Structural Fat Graft
Birgfeld and Heike, 2012 37
• HFM is a highly variable condition which requires and
experienced physician and geneticist collaboration for
• Further genetic studies are required to determine the
etiology of this condition
• Graham A. 2003. Development of the Pharyngeal Arches. American Journal of Medical Genetics 119A:251–256
• Santagati, F., Rijli, F. M., 2003. Cranial neural crest and the building of the vertebrate head. Nat Rev Neurosci. 4, 806-18.
• Craig B. Birgfeld, Carrie Heike, 2012. Craniofacial Microsomia. Semin Plast Surg. 26:91–104.
• S. Gimelli & C. Cuoco & P. Ronchetto & G. Gimelli & E. Tassano, 2013. Interstitial deletion 14q31.1q31.3 transmitted from a mother to her
daughter, both with features of hemifacial microsomia. J Appl Genetics. 54:361–365.
• Passos-Bueno, M. R., Ornelas, C. C., & Fanganiello, R. D. (2009). Syndromes of the first and second pharyngeal arches: A review. Am J Med
Genet A. 149A(8), 1853-1859.
• Pen-Hua Su, Ju-Shan Yu, Jia-Yuh Chen, Suh-Jen Chen, Shuan-Yow Li and Hsiao-Neng Chen, 2007. Mutations and new polymorphic changes in the
TCOF1 gene of patients with oculo–auriculo–vertebral spectrum and Treacher–Collins syndrome. Clinical Dysmorphology. Vol 16 No 4.
• Karina Haratz, Chana Vinkler, Dorit Lev, Letizia Schreiber, Gustavo Malinger, 2011. Hemifacial Microsomia with Spinal and Rib Anomalies:
Prenatal Diagnosis and Postmortem Confirmation Using 3-D Computed Tomography Reconstruction. Fetal Diagn Ther. 30:309–313.
• D. Kelberman, J. Tyson, D. C. Chandler, A. M. McInerney, J. Slee, D. Albert, A. Aymat, M. Botma, M. Calvert, J. Goldblatt, E. A. Haan, N. G.
Laing, J. Lim, S. Malcolm, S. L. Singer, R. M. Winter, M. Bitner-Glindzicz, 2001. Hemifacial microsomia: progress in understanding the genetic
basis of a complex malformation syndrome. Hum Genet. 109 :638–645
• Sven Fischer, Hermann-Josef Ludecke, Dagmar Wieczorek, Stefan Bohringer, Gabriele Gillessen-Kaesbach and Bernhard Horsthemke, 2006.
Histone acetylation dependent allelic expression imbalance of BAPX1 in patients with the oculo-auriculo-vertebral spectrum. Human Molecular
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• Abigail S. Tucker, Robert P. Watson, Laura A. Lettice, Gen Yamada and Robert E. Hill, 2004. Bapx1 regulates patterning in the middle ear:
altered regulatory role in the transition from the proximal jaw during vertebrate evolution. Development 131, 1235-1245.
• Craig T. Miller1, Deborah Yelon, Didier Y. R. Stainier and Charles B. Kimmel, 2003. Two endothelin 1 effectors, hand2 and bapx1, pattern
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• R. R. J. Cousley and M. L. Calvert, 1997. Current concepts in the understanding and management of hemifacial microsomia. British Journal of
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• Lora Mishra, Satya Ranjan Misra, Manoj Kumar, Ramanupam Tripathy, 2013. Hemifacial Microsomia: A Series of Three Case Reports. Journal of
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