eMedicine Specialties > Pediatrics: Genetics and Metabolic Disease > Genetics

Mandibulofacial Dysostosis (Treacher Collins Syndrome): Differential Diagnoses & Workup

Author: Marie M Tolarova, MD, PhD, DSc, Professor and Executive Director, UOP Craniofacial Team, Cleft Prevention Program, Department of Orthodontics, University of the Pacific School of Dentistry
Coauthor(s): Granger B Wong, MD, DMD, FACS, Associate Professor of Surgery, Division of Plastic and Reconstructive Surgery, University of California Davis School of Medicine; Surendra Varma, MD, Vice-Chairman and Program Director, University Distinguished Professor, Department of Pediatrics, Texas Tech University School of Medicine
Contributor Information and Disclosures

Updated: Nov 24, 2009

Differential Diagnoses

Other Problems to Be Considered

Consider the following 3 conditions in the differential diagnoses of mandibulofacial dysostosis (Treacher Collins syndrome):

  • Acrofacial dysostosis, type Nager (preaxial acrofacial dysostosis) is associated with facial features nearly identical to those of Treacher Collins Syndrome. The cleft palate is more frequent, and mandibular growth is usually more severely affected. Lower-lid colobomas are rare. The radial rays are affected, and patients may present with hypoplastic or absent thumbs, radioulnar synostosis, and/or radius and 1 or more metacarpal bones that are hypoplastic or absent. Preaxial acrofacial dysostosis, also known as Nager syndrome, is genetically heterogenous. Autosomal dominant and autosomal recessive patterns have been suggested. Gorlin pointed out that apparent recessive inheritance could represent a nonpenetrance or a gonadal mosaicism.1
  • Oculoauriculovertebral spectrum, including Goldenhar syndrome, should not create a diagnostic problem when the full spectrum is present. The phenotype consists of epibulbar dermoids of the eye, preauricular tags, vertebral defects, and facial underdevelopment.17 Closely examine minimal expression and, if possible, also examine first-degree relatives.
  • X-linked dominant maxillofacial dysostosis consists of bilateral hypoplasia of malar bones, downward-slanting palpebral fissures without colobomas, maxillary hypoplasia, open bite, and relative mandibular prognathism.

Workup

Laboratory Studies

  • Midtrimester ultrasonography can detect facial dysmorphology and, because of its noninvasive quality, is preferred to fetoscopy, which greatly aided prenatal diagnoses in the 1980s.18,19 The images below are examples of fetal findings.

  • Anteroposterior view of 19-week-old fetus with Tr...

    Anteroposterior view of 19-week-old fetus with Treacher Collins syndrome. Diagnosis was confirmed based on fetoscopy images. Tolarova M, Zwinger A. The use of fetoscopy by inborn morphological anomalies. Acta Chir Plast. 1981;23(3):139-51.

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    Anteroposterior view of 19-week-old fetus with Tr...

    Anteroposterior view of 19-week-old fetus with Treacher Collins syndrome. Diagnosis was confirmed based on fetoscopy images. Tolarova M, Zwinger A. The use of fetoscopy by inborn morphological anomalies. Acta Chir Plast. 1981;23(3):139-51.


  • Lateral view of 19-week-old fetus with Treacher C...

    Lateral view of 19-week-old fetus with Treacher Collins syndrome. Diagnosis was confirmed based on fetoscopy images. Tolarova M, Zwinger A. The use of fetoscopy by inborn morphological anomalies. Acta Chir Plast. 1981;23(3):139-51.

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    Lateral view of 19-week-old fetus with Treacher C...

    Lateral view of 19-week-old fetus with Treacher Collins syndrome. Diagnosis was confirmed based on fetoscopy images. Tolarova M, Zwinger A. The use of fetoscopy by inborn morphological anomalies. Acta Chir Plast. 1981;23(3):139-51.

  • Mutations of the TCOF1 gene 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
    • Neuroophthalmologic 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

Imaging Studies

  • The following imaging studies should be obtained to visualize craniofacial dysmorphology in detail and repeated, as needed, 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 (usually enough for surgical planning)
    • Panoramic radiography
    • Brain MRI for inner auditory canal (IAC) study preferred (If MRI is not available, CT scan may be obtained for IAC.)
  • If the clinical diagnosis of Treacher Collins syndrome is in doubt, radiological assessment can be useful. These tests are more helpful when mild expression is suspected upon clinical evaluation. The occipitomental projection of the skull (Waters view, anteroposterior with the canthomeatal line extended 45° with no inclination of the incident ray) can confirm zygomatic arch hypoplasia or aplasia. Orthopantomography should be used to demonstrate mandibular hypoplasia and changes in mandibular configuration. Temporomandibular joint abnormalities and asymmetry can be evaluated on these orthopantomograms. Roentgenography can also reveal any bony asymmetry in mild cases of Treacher Collins syndrome. If a patient needs any surgical correction or treatment, CT scan or MRI is mandatory.

More on Mandibulofacial Dysostosis (Treacher Collins Syndrome)

Overview: Mandibulofacial Dysostosis (Treacher Collins Syndrome)
Differential Diagnoses & Workup: Mandibulofacial Dysostosis (Treacher Collins Syndrome)
Treatment & Medication: Mandibulofacial Dysostosis (Treacher Collins Syndrome)
Follow-up: Mandibulofacial Dysostosis (Treacher Collins Syndrome)
Multimedia: Mandibulofacial Dysostosis (Treacher Collins Syndrome)
References
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References

  1. Gorlin RJ, Cohen MM Jr, Hennekam RCM. Syndromes of the head and neck, 4th ed. Oxford University Press. 2001.

  2. Rovin S et al. Mandibulofacial dysostosis: A familial study of five generations. J Pediatrics. 1964;65:215-221.

  3. 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. May 1995;121(5):509-14. [Medline].

  4. Posnick JC. Treacher Collins syndrome: perspectives in evaluation and treatment. J Oral Maxilofac Surg. 1997;55:1120-33.

  5. [Guideline] Cunniff C. Prenatal screening and diagnosis for pediatricians. Pediatrics. Sep 2004;114(3):889-94. [Medline].

  6. Poswillo D. The pathogenesis of the Treacher Collins syndrome (mandibulofacial dysostosis). Br J Oral Surg. Jul 1975;13(1):1-26. [Medline].

  7. Sulik KK, Johnston MC, Smiley SJ, et al. Mandibulofacial dysostosis (Treacher Collins syndrome): a new proposal for its pathogenesis. Am J Med Genet. Jun 1987;27(2):359-72. [Medline].

  8. 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].

  9. The Treacher Collins Syndrome Collaborative Group. Positional cloning of a gene involved in the pathogenesis of Treacher Collins syndrome. Nat Genet. Feb 1996;12(2):130-6. [Medline].

  10. 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. Apr 1 1997;94(7):3110-5. [Medline]. [Full Text].

  11. Dixon, M. J. Treacher Collins syndrome. Hum. Molec. Genet. 1996;1391-1396.

  12. Edwards, S. J, Gladwin, A. J, Dixon, M. J. The mutational spectrum in Treacher Collins syndrome reveals a predominance of mutations that create a premature-termination codon. Am. J. Hum. Genet. 1997.;60:515-524.

  13. Horiuchi, K, Ariga, T, Fujioka, H. Treacher Collins syndrome with craniosynostosis, choanal atresia, and esophageal regurgitation caused by a novel nonsense mutation in TCOF1. Am. J. Med. Genet. 2004;128A:173-175.

  14. Lowry RB, Morgan K, Holmes TM, et al. Mandibulofacial dysostosis in Hutterite sibs: a possible recessive trait. Am J Med Genet. Nov 1985;22(3):501-12. [Medline].

  15. Richieri-Costa A, Bortolozo MA, Lauris JR, et al. Mandibulofacial dysostosis: report on two Brazilian families suggesting autosomal recessive inheritance. Am J Med Genet. Jul 1 1993;46(6):659-64. [Medline].

  16. Splendore A, Silva EO, Alonso LG, et al. High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes. Hum Mutat. Oct 2000;16(4):315-22. [Medline].

  17. Cohen MM Jr, Rollnick BR, Kaye CI. Oculoauriculovertebral spectrum: an updated critique. Cleft Palate J. Oct 1989;26(4):276-86. [Medline].

  18. Nicolaides KH, Johansson D, Donnai D, Rodeck CH. Prenatal diagnosis of mandibulofacial dysostosis. Prenat Diagn. May-Jun 1984;4(3):201-5. [Medline].

  19. Tolarova M, Zwinger A. The use of fetoscopy by inborn morphological anomalies. Acta Chir Plast. 1981;23(3):139-51. [Medline].

  20. Thompson JT, Anderson PJ, David DJ. Treacher Collins Syndrome: Protocol Management From Birth to Maturity. J Craniofac Surg. Oct 29 2009;[Medline].

  21. Berry GA. Note on a congenital defect (coloboma?) of the lower lid. R Lond Ophthalmol Hosp Rep. 1889;12:255-257.

  22. Collins ET. Cases of symmetrical congenital notches in the outer part of each lower lid and defective development of the malar bones. Trans Ophthal Soc UK. 1900;20:190-192.

  23. Franceschetti A, Klein D. Mandibulo-facial dysostosis: New hereditary syndrome. Acta Ophthalmol (Kbh). 1949;27:143-224.

  24. Moore MH, Guzman-Stein G, Proudman TW, et al. Mandibular lengthening by distraction for airway obstruction in Treacher-Collins syndrome. J Craniofac Surg. Feb 1994;5(1):22-5. [Medline].

  25. Posnick JC, Ruiz RL. Treacher Collins syndrome: current evaluation, treatment, and future directions. Cleft Palate Craniofac J. Sep 2000;37(5):434. [Medline]. [Full Text].

  26. Williams JK, Maull D, Grayson BH, et al. Early decannulation with bilateral mandibular distraction for tracheostomy-dependent patients. Plast Reconstr Surg. Jan 1999;103(1):48-57; discussion 58-9. [Medline].

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Further Reading

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Keywords

Treacher Collins syndrome, TCS, Treacher Collins-Franceschetti syndrome 1, Franceschetti-Zwahlen-Klein syndrome, dysostosis mandibulofacialis, mandibulofacial dysostosis, craniofacial growth, craniofacial structure growth, treatment, diagnosis, symptoms

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Contributor Information and Disclosures

Author

Marie M Tolarova, MD, PhD, DSc, Professor and Executive Director, UOP Craniofacial Team, Cleft Prevention Program, Department of Orthodontics, University of the Pacific School of Dentistry
Marie M Tolarova, MD, PhD, DSc is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American Society of Human Genetics, and International Association for Dental Research
Disclosure: Nothing to disclose.

Coauthor(s)

Granger B Wong, MD, DMD, FACS, Associate Professor of Surgery, Division of Plastic and Reconstructive Surgery, University of California Davis School of Medicine
Granger B Wong, MD, DMD, FACS is a member of the following medical societies: American Society of Plastic and Reconstructive Surgery
Disclosure: Nothing to disclose.

Surendra Varma, MD, Vice-Chairman and Program Director, University Distinguished Professor, Department of Pediatrics, Texas Tech University School of Medicine
Surendra Varma, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American Diabetes Association, American Medical Association, American Thyroid Association, Endocrine Society, Medical Group Management Association, New York Academy of Sciences, Sigma Xi, Society for Pediatric Radiology, Southern Society for Pediatric Research, and Texas Medical Association
Disclosure: Nothing to disclose.

Medical Editor

Elaine H Zackai, MD, Professor of Pediatrics, Professor of Obstetrics and Gynecology, Professor of Pediatrics in Human Genetics, University of Pennsylvania School of Medicine; Director, Clinical Genetics Center, University of Pennsylvania; Senior Physician and Director of Clinical Genetics, The Children's Hospital of Philadelphia
Elaine H Zackai, MD is a member of the following medical societies: American Cleft Palate/Craniofacial Association, American College of Medical Genetics, and American Society of Human Genetics
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Margaret M McGovern, MD, PhD, Professor and Chair of Pediatrics, Stony Brook University, New York
Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics and American Society of Human Genetics
Disclosure: Genzyme Grant/research funds PI

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Bruce Buehler, MD, Professor, Department of Pediatrics, Pathology and Microbiology, Executive Director, Hattie B Munroe Center for Human Genetics, University of Nebraska Medical Center
Bruce Buehler, MD is a member of the following medical societies: American Academy for Cerebral Palsy and Developmental Medicine, American Academy of Pediatrics, American Association on Mental Retardation, American College of Medical Genetics, American College of Physician Executives, American Medical Association, and Nebraska Medical Association
Disclosure: Nothing to disclose.

 
 
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