You are on page 1of 21

Mandibulofacial dysostosis,

also known as Treacher


Collins syndrome

Treacher Collins
syndrome
1 in 40,000 to 1 in 70,000 of live
births
Diminished growth of craniofacial
structures derived from the first and
second pharyngeal arch, groove, and
pouch.

Physical Exam
The Face is characteristic.
Abnormalities are usually
present bilaterally
and symmetrically.

Skull:
Malar bones, zygomatic process of frontal
bone, lateral pterygoid plates, paranasal
sinuses, and mandibular condyles are
hypoplastic.
The mastoids are not pneumatized.
The lateral margins of the orbits may be
defective, and the orbits are hyperteloric.
The cranial base is progressively kyphotic.
The calvaria are essentially normal.

Eyes:
The palpebral fissures are short and
slope laterally downward.
In the outer third of
the lower lid, a
coloboma is
present, and the
cilia (eyelashes)
may be deficient
medially from the

Ears:
The pinnae are often malformed, crumpled forward, or misplaced
toward the angle of the mandible
Extra ear tags and
blind fistulas may develop
anywhere between the tragus
and the angle of the mouth

Ears:
Absence of the middle ear and tympanic
spaces are present, resulting in a conductive
hearing loss.
The inner ears are normal

Nose:
The nose appears
large because of the
lack of malar
development and
hypoplastic
supraorbital ridges.

Mouth and throat :

A Cleft palate is found in one third of the


patients, and congenital palatopharyngeal
incompetence (foreshortened, immobile,
or absent soft palate)
o Submucous cleft palate is found in an
additional one third of patients.

The parotid glands are missing or


hypoplastic.
Pharyngeal hypoplasia is a constant
finding.

Other features:
Mental status: Intelligence is usually normal
Developmental delay may be secondary to
undiagnosed hearing loss.
Dysfunctional symptoms: Hypoplasia and a
retropositioned tongue
Difficulties with swallowing and feeding (caused
by musculoskeletal underdevelopment and a
cleft palate)
Conductive hearing loss (caused by
maldevelopment of the auditory canal and
middle ear ossicles)
Impaired vision (caused by under developed
lateral orbit and extraocular muscles)

Causes:
1. Embryology:
Failure of neural crest cells to migrate into
the first and second branchial arches leads
to dysplasia, hypoplasia, or aplasia of the
musculoskeletal
derivatives
of
these
arches. Therefore, the abnormalities are
bilateral and symmetrical.

The critical period occurs approximately


between the sixth and seventh week of
embryonal development.

Causes
Genetic

Autosomal dominant
Approximately 60% of cases represent fresh
mutations.
May be associated with exposure of a
teratogenic dose of vitamin A (animal studies)
Can be caused by mutations in
theTCOF1gene.
o TCOF1was mapped to chromosome bands 5q31.333.3.

DDx
Nager Syndrome (Preaxial acrofacial dysostosis)
o Facial features nearly identical to those of Treacher Collins Syndrome.
o Cleft palate, mandibular growth (more severe), hypoplastic or
absent thumbs, radioulnar synostosis, lower eyelid colobomas are
rare

Oculoauriculovertebral spectrum, including Goldenhar


syndrome.
o Epibulbar dermoids of the eye, preauricular tags, vertebral defects, and
facial underdevelopment.

X-linked dominant maxillofacial dysostosis


o B/L hypoplasia of malar bones, downward-slanting palpebral fissures
without colobomas, maxillary hypoplasia, open bite, and relative
mandibular prognathism.

Work Up
Midtrimester ultrasonography can
detect facial dysmorphology and,
because of its noninvasive quality, is
preferred to fetoscopy

Work Up
Mutations of theTCOF1gene can be
detected as single-nucleotide
polymorphisms. Thus, prenatal diagnosis
is possible but not yet clinically available.
A prenatal diagnosis requires the
following:
Blood samples from family members
Fetal cells obtained via chorionic villi
sampling (performed at 10-11 weeks'
gestation) or via amniocentesis (performed
at 16-17 weeks' gestation)

Assessment and
monitoring of postnatal
functions

Pulse oximeter
Monitoring of hemoglobin saturation with oxygen
Assessment of feeding efficiency
Audiologic testing
Neuro-ophthalmologic assessment
Full craniofacial CT scan (axial and coronal slices,
from the top of the skull through the cervical
spine)
Evaluation and genetic diagnosis by a medical
geneticist

Radiology (for surgical


planning):
Anteroposterior and lateral cephalography
Full craniofacial CT scan (axial and coronal slices
from the top of the skull through the cervical
spine)
As follow-up, CT scans from orbits through
mandible
Panoramic radiography
Brain MRI for inner auditory canal (IAC) study
preferred (If MRI is not available, CT scan may be
obtained for IAC.)

Treatment
Treatment of mandibulofacial dysostosis
(Treacher Collins syndrome) is lengthy
and requires a multidisciplinary approach
focused on treatment of symptoms.
In newborns with mandibulofacial
dysostosis, immediate attention to
airway and swallowing inadequacies is
critical

Treatment
Severe airway inadequacy tracheostomy is performed
o until the lower jaw has sufficiently grown or until alveolar
distraction is performed (May take several years)

Otherwise, special positioning of the infant may be sufficient


Severe swallowing difficulty introduce feeding to
ensure adequate caloric intake and hydration.
Substantial conductive hearing loss Fit hearing
aidshortly after birth
Important for the development of the infant's communication
skills and for the normal bonding process within the family

Family-to-family support has proven to be of great


psychological value

References

Gorlin RJ, Cohen MM Jr, Hennekam RCM. Syndromes of the head and neck, 4th ed.Oxford
University Press. 2001.
Rovin S et al. Mandibulofacial dysostosis: A familial study of five generations.J Pediatrics. 1964.
65:215-221.
Marres HA, Cremers CW, Dixon MJ, et al. The Treacher Collins syndrome. A clinical, radiological,
and genetic linkage study on two pedigrees.Arch Otolaryngol Head Neck Surg. 1995 May.
121(5):509-14.[Medline].
Posnick JC. Treacher Collins syndrome: perspectives in evaluation and treatment.J Oral
Maxilofac Surg. 1997. 55:1120-33.
[Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians.Pediatrics. 2004 Sep.
114(3):889-94.[Medline].
Poswillo D. The pathogenesis of the Treacher Collins syndrome (mandibulofacial dysostosis).Br J
Oral Surg. 1975 Jul. 13(1):1-26.[Medline].
Sulik KK, Johnston MC, Smiley SJ, et al. Mandibulofacial dysostosis (Treacher Collins syndrome):
a new proposal for its pathogenesis.Am J Med Genet. 1987 Jun. 27(2):359-72.[Medline].
Wiley MJ, Cauwenbergs P, Taylor IM. Effects of retinoic acid on the development of the facial
skeleton in hamsters: early changes involving cranial neural crest cells.Acta Anat (Basel). 1983.
116(2):180-92.[Medline].
The Treacher Collins Syndrome Collaborative Group. Positional cloning of a gene involved in the
pathogenesis of Treacher Collins syndrome.Nat Genet. 1996 Feb. 12(2):130-6.[Medline].
Wise CA, Chiang LC, Paznekas WA, et al. TCOF1 gene encodes a putative nucleolar
phosphoprotein that exhibits mutations in Treacher Collins Syndrome throughout its coding
region.Proc Natl Acad Sci U S A. 1997 Apr 1. 94(7):3110-5.[Medline].[Full Text].
Dixon, M. J. Treacher Collins syndrome.Hum. Molec. Genet. 1996. 1391-1396.
Lines MA, Huang L, Schwartzentruber J, Douglas SL, Lynch DC, Beaulieu C, et al.
Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial
Dysostosis with Microcephaly.Am J Hum Genet. 2012 Feb 10. 90(2):369-77.[Medline].[Full
Text].

Thank You