Treacher Collins syndrome

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Treacher Collins syndrome
Classification and external resources
ICD-10Q75.4
ICD-9756.0
OMIM154500
DiseasesDB13267
MedlinePlus001659
eMedicineplastic/183
MeSHD008342
 
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Treacher Collins syndrome
Classification and external resources
ICD-10Q75.4
ICD-9756.0
OMIM154500
DiseasesDB13267
MedlinePlus001659
eMedicineplastic/183
MeSHD008342

Treacher Collins syndrome (TCS), also known as Treacher Collins–Franceschetti syndrome,[1] or mandibulofacial dysostosis[2] is a rare autosomal dominant congenital disorder characterized by craniofacial deformities, such as absent cheekbones.[3]:577 Treacher Collins syndrome is found in about 1 in 50,000[4] births. The typical physical features include downward slanting eyes, micrognathia (a small lower jaw), conductive hearing loss, underdeveloped zygoma, drooping part of the lateral lower eyelids, and malformed or absent ears.

Eponym[edit]

It is named after Edward Treacher Collins (1862–1932), the English surgeon and ophthalmologist who described its essential traits in 1900.[5] In 1949, Adolphe Franceschetti and David Klein described the same condition on their own observations as mandibulofacial dysostosis. The term mandibulofacial dysostosis is used to describe the clinical features.[6]

Cause[edit]

Mutations in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins syndrome. TCOF1 gene mutations are the most common cause of the disorder, accounting for 81 to 93 percent of all cases. POLR1C and POLR1D gene mutations cause an additional 2 percent of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into new proteins, which is essential for the normal functioning and survival of cells. Mutations in the TCOF1, POLR1C, or POLR1D gene reduce the production of rRNA. Researchers speculate that a decrease in the amount of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. The abnormal cell death could lead to the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Kind of mutation[edit]

TCOF1 is the only gene currently known to be associated with TCS, a mutation in this gene being found in 90-95% of the individuals with TCS.[7][8] However in some individuals with typical symptoms of TCS, mutations in TCOF1 have not been found.[9] Investigation of the DNA has resulted in the identification of the kind of mutations found in TCOF1. The majority of mutations are small deletions or insertions, though splice site and missense mutations also been identified.[7][10][11][12] Mutation analysis has unveiled more than 100 disease-causing mutations in TCOF1, which are mostly family specific mutations. Only one recurrent mutation accounts for approximately 17% of the cases.[13]

Treacher Collins syndrome is inherited in an autosomal-dominant pattern.

Function of the TCOF1 gene[edit]

TCOF1 codes for a relatively simple, nucleolar protein called Treacle.[8] Mutations in TCOF1 lead to haploinsufficiency of the Treacle protein.[14] Haploinsufficiency occurs when a diploid organism has only one functional copy of a gene, because the other copy is inactivated by a mutation. Thereby the other functional gene does not produce enough of a gene-product to have the expected function, resulting in an abnormal disease state. Haploinsufficiency of the Treacle protein leads to a depletion of the neural crest cell precursor, which leads to a reduced number of crest cells migrating to the first and second pharyngeal arches. These crest cells play an important role in the development of the craniofacial appearance.[15][10] So down regulation of Treacle expression results in craniofacial defects and growth retardation.

Genetic counselling[edit]

TCS is inherited in an autosomal dominant manner and the penetrance of the affected gene is almost complete.[16] On the other hand some recent investigations described some rare cases in which the penetrance in TCS was not complete. Causes may be a variable expressivity, an incomplete penetrance [17] or germline mosaicism.[18] Only 40% of the mutations are inherited. The remaining 60% is a result of a de novo mutation.[19] In the outcome of the disease there is a lot of inter- and intrafamilial variability. This suggests that when an affected child is born, it is important to investigate the parents if the affected gene is present. It could be possible that a parent has a mild and undiagnosed TCS. In this case the risk of having another affected child is 50%. If the parents do not have the affected gene, the recurrence risk appears to be low.[16] In following generations the severity of the clinical symptoms increases.[11]

Signs[edit]

The incidence of this syndrome is 1 in 50,000 live births. The presentation of symptoms in people with Treacher Collins Syndrome varies. Some individuals may be so mildly affected that they remain undiagnosed, others can have severe facial involvement and life-threatening airway compromise.[20] Most of the features of TCS are bilateral and are already recognisable at birth. The most life threatening problem of individuals with TCS is a constricted airway, since this can give problems with breathing.

Patients are mostly characterized by the following abnormalities:

The presence of an abnormally shaped skull is not distinctive for Treacher Collins Syndrome but brachycephaly with bitemporal narrowing is sometimes observed.[21]

Dental anomalies are seen in 60% of TCS patients. These anomalies consist in tooth agenesis (33%), enamel disformaties (20%) and malplacement of the maxillary first molars (13%). In some cases dental anomalies in combination with mandible hypoplasia result in a malocclusion, this can lead to problems with food intake and the ability to close the mouth.

Some features related to TCS are seen less frequently:[7]

Facial deformity is nowadays still associated by the general public with developmental delay, and lesser intelligence, but intelligence of patients with TCS is usually normal. The psychological and social problems associated with facial deformity may affect quality of life in a number of patients.

Diagnosis[edit]

The diagnosis of Treacher Collins Syndrome relies upon clinical and radiographic findings.

Clinical findings[edit]

There is a set of typical symptoms within Treacher Collins Syndrome. Those symptoms can be detected by a critical clinical view. The wide spectrum of diseases which have similar characteristics make it sometimes difficult to diagnose TCS.[25] The OMENS classification was developed as a comprehensive and stage-based approach to differentiate the diseases. This acronym describes five distinct dysmorphic manifestations, namely O; orbital asymmetry, M; mandibular hypoplasia, E; auricular deformity, N; nerve development and S; soft-tissue disease. The table below shows the OMENS classification in more detail.[26]

Orbit

Mandible

  1. 2A: glenoid fossa in anatomical acceptable position
  2. 2B: Temperomandibular joint inferiorly (TMJ), medially, anteriorly displaced, with severely hypoplastic condyle

Ear

Facial Nerve

Soft tissue

Radiological findings[edit]

Radiologic manifestations can be used to confirm the diagnosis. Imaging evaluation consists of X-rays (radiographs), CT scans, MRI, and/or ultrasound.

Radiographs[edit]

There are a few techniques which are used to confirm the diagnosis in TCS. An OPG is a panoramic dental X-ray of the upper and lower jaw. It shows a two-dimensional image from ear to ear. Particularly OPG facilitate an accurate post-operative follow-up and monitoring of bone growth under a mono or double-distractor treatment. Thereby some TCS features could be seen on orthopantogram, but there are better techniques to include the whole spectrum of TCS abnormalities instead of showing only the jaw abnormalities.[25] Another method of radiographic evaluation is taking a X-ray image of the whole head. The lateral cephalometric radiograph in TCS shows hypoplasia of the facial bones, like the malar bone, mandible and the mastoid.[25] Finally the occipitomental radiographs are used to detect hypoplasia or discontinuity of the zygomatic arch.[27]

CT-scan[edit]

A temporal bone CT using thin slices makes it possible to diagnose the degree of stenosis and atresia of the external auditory channel, the status of the middle ear cavity, the absent or dysplastic and rudimentary ossicles or the inner ear abnormalities such as a deficient cochlea. Two dimensional and 3D CT reconstructions with VRT and bone and skin-surfacing are helpful for more accurate staging and the 3-D planning of mandibular and external ear reconstructive surgery.

Differential diagnosis[edit]

There are other diseases which have similar characteristics as Treacher Collins Syndrome. In the differential diagnosis one should consider the acrofacial dysostoses. The facial appearance resembles that of Treacher Collins Syndrome, but there are additional limb abnormalities in those patients. Examples of these diseases are the Nager Syndrome and the Miller Syndrome. The oculoauriculovertebral spectrum should also be considered in the differential diagnosis. An example is Hemifacial Microsomia which primarily affects development of the ear, mouth, and mandible. This anomaly may occur bilaterally. Another disease which belongs to this spectrum is the Goldenhar Syndrome, which includes vertebral abnormalities, epibulbar dermoids and facial deformities.[28]

Management[edit]

The treatment of individuals affected by TCS needs a multidisciplinary approach and may involve the intervention of different professionals. The primary concerns in individuals with TCS are breathing and feeding problems, which are a consequence of the hypoplasia of the mandibula and the obstruction of the hypopharynx by the tongue. Sometimes even a tracheostomy is necessary to maintain an adequate airway.[29] Also a gastrostomy could be necessary to assure an adequate caloric intake while protecting the airway. Surgery to restore a normal structure of the face is normally performed at defined ages, depending on the development state.[30]

An overview of the present guidelines:

  1. Type I (mild) and Type IIa (moderate) 13–16 years
  2. Type IIb (moderate to severe malformation) at skeletal maturity
  3. Type III (severe) 6–10 years

Hearing loss[edit]

Hearing loss in Treacher Collins Syndrome is caused by deformed structures in the outer and middle ear. The hearing loss is generally bilateral with a conductive loss of about 50-70 dB. Even in cases with normal auricles and open external auditory canals, the ossicular chain is often malformed.[36]

Attempts to surgically reconstruct the external auditory canal and improve hearing in children with Treacher Collins Syndrome have not yielded positive results.[37] Auditory rehabilitation with BAHA or a conventional bone conduction aid has proven preferable to surgical reconstruction.[33]

For patients with Treacher Collins Syndrome, Bone Anchored Hearing Aid(BAHA) provides several advantages:

BAHA is a solution that overcomes a conductive hearing loss resulting from the auricular malformations seen in Treacher Collins Syndrome. Great improvements in language development have been reported after Baha fittings. Also, the Baha Softband provides the possibility of early aiding that is so important in this particular patient group[38][39]

For Treacher Collins syndrome patients a proper management of symptoms and needs results in a life expectancy that approximates that of the general population.

Media portrayals[edit]

A July 1977 New York Times article[42] that was reprinted in numerous newspapers nationwide over the ensuing weeks, brought this malady to many people's attention for the first time.

While a student at Temple University, Bob Saget directed an 11-minute documentary about his 7 year-old nephew Adam who was undergoing cranial surgery to correct his symptoms of Treacher Collins syndrome. The documentary, titled Through Adam's Eyes, went on to win a 1978 Student Academy Award.

Treacher Collins syndrome was featured in the 2005 Discovery Channel documentary, Unmasked: Treacher Collins Syndrome. As of 2008, it was still being shown on Discovery Health and the TLC channels.

The disorder was featured on the show Nip/Tuck, in the episode "Blu Mondae."[43]

TLC's Born Without a Face[44] features Juliana Wetmore, who was born with the most severe case in medical history of this syndrome and is missing 30%–40% of the bones in her face.[44]

In 2010, BBC Three documentary Love Me, Love My Face[45] covered the case of a man, Jono Lancaster, with the condition. In 2011, BBC Three returned to Jono to cover his and his partner Laura's quest to start a family,[2] in So What If My Baby Is Born Like Me?,[46] which first aired as part of a BBC Three season of programmes on parenting.[47] The first film was replayed on BBC One shortly ahead of the second film's initial BBC Three broadcast. Lancaster's third BBC Three film, Finding My Family on Facebook,[48] which looked at adoption, aired in 2011.

A young man with TCS was one of a number of people with various face/body-altering medical conditions or injuries to take part in Katie Piper's 2011 Channel 4 television series Katie: My Beautiful Friends.

A boy, Nathaniel Newman, with TCS was one of the subjects on National Geographic Channel series Taboo, in the episode, Ugly.

Released on February 14, 2012, the book Wonder is about a boy with the condition.

See also[edit]

References[edit]

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  3. ^ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology. (10th ed.). Saunders. ISBN 0-7216-2921-0.
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  33. ^ a b Marres, HA (2002). "Hearing loss in the Treacher-Collins syndrome.". Advances in oto-rhino-laryngology 61: 209–15. doi:10.1159/000066811. PMID 12408086. 
  34. ^ a b Zhang, Zhiyong; Niu, Feng; Tang, Xiaojun; Yu, Bing; Liu, Jianfeng; Gui, Lai (1 September 2009). "Staged Reconstruction for Adult Complete Treacher Collins Syndrome". Journal of Craniofacial Surgery 20 (5): 1433–1438. doi:10.1097/SCS.0b013e3181af21f9. PMID 19816274. 
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  37. ^ a b Marres, HA; Cremers, CW; Marres, EH (1995). "Treacher-Collins syndrome. Management of major and minor anomalies of the ear.". Revue de laryngologie - otologie - rhinologie 116 (2): 105–8. PMID 7569369. 
  38. ^ a b Verhagen, C.V.M.; Hol, M.K.S.; Coppens-Schellekens, W.; Snik, A.F.M.; Cremers, C.W.R.J. (1 October 2008). "The Baha Softband". International Journal of Pediatric Otorhinolaryngology 72 (10): 1455–1459. doi:10.1016/j.ijporl.2008.06.009. PMID 18667244. 
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  40. ^ Granström, G; Tjellström, A (1997 Apr). "The bone-anchored hearing aid (BAHA) in children with auricular malformations.". Ear, nose, & throat journal 76 (4): 238–40, 242, 244–7. PMID 9127523. 
  41. ^ Thomas, J (1996). "Speech and voice rehabilitation in selected patients fitted with a bone anchored hearing aid (BAHA).". The Journal of laryngology and otology. Supplement 21: 47–51. PMID 9015449. 
  42. ^ "Surgical Teamwork Gives Disease Victims a New Life", Donald G. McNeil, Jr., July 26, 1977, page L31.
  43. ^ Nip/Tuck: Blu Mondae - TV.com
  44. ^ a b First Coast News: Local Family Has Daughter Born Without a Face
  45. ^ BBC programme page for Love Me, Love My Face
  46. ^ BBC programme page for So What If My Baby...
  47. ^ BBC Three Bringing Up Britain season
  48. ^ BBC Programmes: 'Finding My Family on Facebook'

External links[edit]