1. MANDIBULOFACIAL DYSOSTOSIS
Corina Radu, DMD
CNMC, November 2000

2. Definition
Mandibulofacial dysostosis- involves structures derived from the 1st and 2nd pharyngeal arch, groove and pouch
an autosomal dominant disorder characterized by certain facial features including receding chin and malformed ears

3. Treacher Collins syndrome, Franceschetti-Zwahlen-Klein Syndrome
BACKGROUND:
described by Thomson and Toynbee (1846), Berry (1889), Treacher Collins (1900)
Franceschetti et al (1940’s) published extensive reviews of the disorder and coined the term mandibulofacial dysostosis
Although the syndrome was probably first described by Thomson and Toynbee in , credit for its discovery is given to Berry, or especially to Treacher Collins, who described the essential components of the syndrome in 1900.

4. - familial-autosomal dominant with high penetrance
EPIDEMIOLOGY:
Incidence?
Age of onset: at birth
risk factors:
- familial-autosomal dominant with high penetrance
chrom.#: 5q
gene:?
- M= F
- ? Advanced paternal age
PATHOGENESIS:
50-60% of new cases represent de novo mutations
there may be an autosomal recessive form
The syndrome has autosomal dominant inheritance with variable expressivity. A number of families have expressed the syndrome in several generations.
Franceschetti et al, in a review of 63 cases, found 27 with a family history of the syndrome.
Dixon et al located the gene for the syndrome: 5q31-34
Among the roughly 60% that represent new mutations, it has been shown that the fathers tend to be older.

5. CLINICAL FEATURES FACIES: characteristic, with bilateral and
usually symmetrical abnormalities
the face is narrow
downward sloping palpebral fissures
(89%), depressed cheeckbones,
malformed pinnae, receding chin,
and large downturned mouth
~ 25% projection of scalp hair
onto the lateral cheek

6. Nose
the nose appears large because of the lack of malar development and hypoplastic supraorbital rims and zygomas. The nasofrontal angle is obliterated, the nares are often narrow.

7. Mandibulofacial dysostosis
Note downslanting palpebral fissures, coloboma of the outer third of lower eyelids, poor malar and mandibular development, bizzarre pinnae.

8. Skull
Normal calvaria, but w. poorly developed supraorbital ridges (radiographic studies)
the cranial base is progressively kyphotic
malar hypoplasia-sunken cheeckbones 81%
hypoplastic zygomatic processes of the frontal bone, lateral pterygoid plates and muscles

9. Skull the mastoids are frequently sclerotic
the paranasal sinuses are small/absent
the lower margin of the orbit may be defective and the infraorbital foramen is usually absent
the mdb condyle is severely hypoplastic, covered with hyaline cartilage rather than fibrocartilage

10. Eyes
visual loss (37%)
Short palpebral fissures, sloped laterally downward (asymmetric)
coloboma (fissure or gap) present in the outer third of the lower lid 75%
partial or total absence of the lower eyelashes medial to the coloboma (53%)
lower lacrimal point may be absent

12. Close-up of eye in different patients showing absence of cilia on lower eyelid. Note coloboma of lower lid on the Left image.

13. Ears deformed pinnas external ear canal defect (36%)
inner ears are normal
auditory ossicles and cochlear and vestibular apparatus: malformed/ absent
microtia (malformation of the auricles)-77%
hearing loss (conductive/sensorineural) 40%
extra ear tags and blind fistulas between the corners of the mouth and the tragus
The pinnae are often malformed, crumpled forward, or misplaced toward the angle of the mandible. In the survey of Stovin et al of 51 of 63 pts had anomalous pinnae with meatal atresia and over one third had absence of the external auditory ossicle defect accompanied by bilateral conductive hearing loss. Kolar et al found microtia in 60%.
Radiographic and surgical studies have shown agenesis or hypoplasia of the mastoid and mastoid antrum, absence of the external auditory canal, narrowing or agenesis of the middle ear cleft, agenesis or malformation of the malleus and/or incus, monopodal stapes, absence of the stapes and oval window, deformed suprastructure of the stapes, complete absence of the midle ear and epitympanic space. The space may be filled with connective tissue.

14. Mental Status Intelligence is usually normal
Stovin et al found 4/out of 63 pts mentally deficient
others: mild retardation (possible due to hearing loss)

15. Oral Findings Cleft palate (28-35); rarely cleft-lip-palate
congenital palatopharyngeal incompetence (agenesis/foreshortened soft palate, submucous palatal cleft,immobile soft palate) 30-40%
uni-/bilateral macrostomia (15%)
deficient elevator muscles of the upper lip
dental maloclusion
widely-spaced, hypoplastic/ displaced teeth

16. Oral Findings mdb hypoplasia (receding chin, micrognathia)-78%
absent/ hypoplastic parotid salivary glands
pharyngeal hypoplasia
Rx studies: malformed condyle, short neck
concave undersurface of the mdb body
deficient mdb ramus, obtuse angle
flat/ aplastic coronoid and condyloid processes, without articular eminence

17. Complications
Respiratory difficulties (upper airway obstruction, obstructive sleep apneea) due to midface and mdb hypoplasia
feeding difficulties in the newborn period
deafness
visual loss due to refractive errors, anisometropia, strabismus, and/or ptosis

18. Investigations Skull X-Rays mandibular hypoplasia
hypoplasia of the zygomatic arch
Laboratory aids:
midtrimester sonographic diagnosis
fetoscopy-prenatal dg

19. Lat ceph showing extremely steep mdb plane angle, antegonial notching, and mdb deficiency. Soft tissue demonstrates prominent nasal contour, acute nasio-labial angle, and lip incompetence.
Panorex X-Ray showing prominent antegonial notching and open bite.

20. Management Supportive Multidisciplinary approach genetic counseling
hearing aids if indicated

21. Prognosis
Pharyngeal hypoplasia, a constant finding, may explain cases of neonatal death
normal life span
normal intelligence

22. Differential Diagnosis
NAGER ACROFACIAL DYSOSTOSIS
closely resemblance: hypoplastic/absent thumbs, the radius and ulna may be fused or there may be absence/hypoplasia of the radius and/or one or more metacarpals
lower lid colobomas are rarer, cleft palate more frequent, and the mdb more severely retarded in growth than in mandibulofacial dysostosis

23. Differential Diagnostic
MAXILLOFACIAL DYSOSTOSIS- bilateral hypoplasia of malar bones, downward-slanting palpebral fissures w/o colobomas, maxillary hypoplasia, open bite, relative mdb prognathism (X-linked, dominantly inherited)

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