Treacher Collins Syndrome

Treacher Collins syndrome is a rare genetic condition with autosomal dominant inheritance. Treacher Collins syndrome is also referred to as mandibulofacial dysostosis or Franceschetti syndrome and is characterized by significant craniofacial deformities and conductive hearing loss. Treacher Collins syndrome is strictly a physical disease and does not affect cognition or other spheres of development. Diagnosis is confirmed with genetic testing. Management of the airway, feeding ability, and hearing loss are the primary concerns in the first few years of life. Ultimately, facial reconstructive surgery is needed. Life expectancy is normal.

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Epidemiology and Genetics

Epidemiology

  • Incidence: 1 in 25,000–50,000 live births
  • Women and men equally affected

Genetics

  • Results from a deletion mutation or sequence variation impairing proteins and rRNA that play a role in early development
  • Most commonly due to loss of function mutation on the TCOF gene on chromosome 5
    • Autosomal dominant (incomplete penetrance)
    • 40% of patients have affected parents.
    • 60% of patients have de novo mutations (idiopathic).
  • Less commonly due to mutations in the POLR1C gene (autosomal recessive) and POLR1D gene (autosomal dominant)
  • Neural crest cell dysfunction and abnormal 1st and 2nd pharyngeal arch development →  failure of cartilage, bone, and connective tissues to undergo normal facial development  
    • 1st pharyngeal arch (mandibular arch) contributes to mandible, maxilla, zygomatic bone, and middle ear development.
    • 2nd pharyngeal arch (hyoid arch) also contributes to middle ear development as well as hyoid development.

Clinical Presentation

This syndrome is characterized by a multitude of bilateral and often asymmetric craniofacial structural defects and abnormalities.

Ocular symptoms

  • Abnormal, downward-slanting, short palpebral fissures
  • Coloboma of eyelid (part of upper or lower eyelid is absent)
  • Deficiency of eyelashes

Nasal symptoms

  • Choanal atresia (bony and/or membranous tissue blocks back of nasal passageway) 
  • Hypoplasia or aplasia of the zygomatic arch may make the nose appear larger.

Otologic symptoms

  • Conductive hearing loss
  • Microtia
  • Malformed pinna, low-set
  • Meatal atresia
  • Hypoplasia of incus and malleus plus ankylosis of stapes

Oropharyngeal symptoms

  • Difficulties with swallowing and feeding
  • Cleft palate
  • Pharyngeal hypoplasia
  • Malar hypoplasia
  • Bifid uvula
  • Retro-positioned tongue 
  • Dental anomalies
  • Mandibular retrognathia

Cognitive/behavioral symptoms

  • Cognition is typically normal.
  • Failure to thrive may be seen in young children due to feeding difficulties and under-nutrition.
  • Psychological and social development is typically normal, but challenges may arise due to physical appearance.

Diagnosis

  • History and clinical examination
  • Genetic testing confirms diagnosis: analysis of TCOF1, POLR1D, and POLR1C genes
  • Imaging studies to confirm and determine the extent of abnormalities seen:
    • Skull radiographs, particularly with an occipitomental or Waters’ view: aplasia or hypoplasia of the zygomatic arch and mandibular retrognathia
    • Craniofacial computed tomography (CT): malar hypoplasia
    • Dental radiographs

Management

Craniofacial malformations can result in airway compromise and feeding difficulties, making management of these problems the priority in early years. Once life-threatening issues are resolved, management of hearing loss is imperative for speech development. Surgery is needed for correction of facial abnormalities.

Nutritional management

  • Special cleft palate nursing bottle
  • Manage gastroesophageal reflux 
  • Gastrostomy tube for those incapable of feeding

Surgery

  • Cochlear implants early in life to help facilitate speech development
  • Pediatric plastic surgery is delayed until a significant amount of facial growth has occurred, typically around 7 years of age. 
    • Zygomatic and orbital reconstruction 
    • External ear reconstruction 
    • Middle ear reconstruction 
    • Maxillomandibular reconstruction (done in adolescent years)
  • Oral surgery: cleft palate, cleft lip, bifid uvula

Other

  • Speech/language therapy
  • Correction of dental abnormalities between 6 and 14 years of age
  • Pediatric ophthalmology evaluation
  • Genetic counseling

Differential Diagnosis

  • Nager syndrome: also called preaxial acrofacial dysostosis, Nager syndrome is a rare genetic condition with mostly autosomal dominant inheritance. Craniofacial malformations are similar to Treacher Collins syndrome. Additionally, patients have defects of the upper extremities, such as underdeveloped or absent thumbs and shortened forearms. Genetic testing can help differentiate this condition from Treacher Collins syndrome. Treatment is similar to that for Treacher Collins syndrome.
  • Miller syndrome: also called postaxial acrofacial dysostosis, a rare genetic condition with autosomal recessive inheritance. Craniofacial malformations are seen, similar to Treacher Collins syndrome. Additionally, patients have supernumerary nipples and upper and lower extremity defects such as missing 5th fingers/toes, shortened forearms, and webbed or fused digits. Genetic testing helps differentiate this condition from other conditions. Management is similar to that for Treacher Collins syndrome.
  • Pierre Robin sequence: refers to a set of maxillofacial malformations that occur due to an abnormality in the embryonic developmental sequence and may or may not be associated with any particular syndrome. Mandibular hypoplasia leads to glossoptosis (posteriorly displaced tongue), which results in abnormal palate development and subsequent U-shaped cleft palate. Diagnosed clinically with possible genetic testing to detect any underlying syndrome. Management is similar to that for Treacher Collins syndrome.

References

  1. Chang, Christopher C. & Steinbacher, Derek M. (2012). Treacher Collins Syndrome. Semin Plast Surg. 26(2): 83–90. doi: 10.1055/s-0032-1320066. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3424693/
  2. Buchanan, Edward P. (2018). Syndromes with craniofacial abnormalities. UpToDate. Retrieved December 1, 2020, from https://www.uptodate.com/contents/syndromes-with-craniofacial-abnormalities?search=mandibulofacial%20dysostosis&source=search_result&selectedTitle=1~23&usage_type=default&display_rank=1
  3. Aljerian, A., & Gilardino, M. S. (2019). Treacher Collins Syndrome. Clinics in plastic surgery, 46(2), 197–205. https://doi.org/10.1016/j.cps.2018.11.005
  4. Plomp, R. G., van Lieshout, M. J., Joosten, K. F., Wolvius, E. B., van der Schroeff, M. P., Versnel, S. L., Poublon, R. M., & Mathijssen, I. M. (2016). Treacher Collins Syndrome: A Systematic Review of Evidence-Based Treatment and Recommendations. Plastic and reconstructive surgery, 137(1), 191–204. https://doi.org/10.1097/PRS.0000000000001896

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