What are the other Names for this Condition? (Also known as/Synonyms)

• Mandibulofacial Dysostosis
• TCS (Treacher Collins Syndrome)
• Treacher Collins-Franceschetti Syndrome (TCOF)

What is Treacher Collins Syndrome? (Definition/Background Information)

• Treacher Collins Syndrome (TCS) is a condition that affects the development of bones and other tissues of the face. The signs and symptoms vary greatly, ranging from almost unnoticeable to severe
• Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Other features may include cleft palate, eye abnormalities, and hearing loss
• Treacher Collins Syndrome may be caused by mutations in the TCOF1, POLR1C, or POLR1D genes. When the TCOF1 or POLR1D gene is responsible, it is inherited in an autosomal dominant manner
• However, about 60% of autosomal dominant cases are due to a new mutation in the gene and are not inherited from a parent. When the POLR1C gene is responsible, it is inherited in an autosomal recessive manner
• In some cases, the genetic cause of Treacher Collins Syndrome is unknown

(Source: Treacher Collins Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Treacher Collins Syndrome? (Age and Sex Distribution)

• Treacher Collins Syndrome is a rare congenital disorder. The presentation of symptoms may occur at birth
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Treacher Collins Syndrome? (Predisposing Factors)

• A positive family history may be an important risk factor, since Treacher Collins Syndrome can be inherited
• Currently, no risk factors have been clearly identified for the syndrome

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Treacher Collins Syndrome? (Etiology)

• Treacher Collins Syndrome (TCS) is caused by changes (mutations) in any of several genes: TCOF1 (in over 80% of cases), POLR1C, or POLR1D
• In a few cases, the genetic cause of the condition is unknown
• These genes appear to play important roles in the early development of bones and other tissues of the face. They are involved in making proteins that help make ribosomal RNA (rRNA)
  • rRNA is a chemical needed to make new proteins that are necessary for normal function and survival of cells
  • Mutations in these genes can reduce the production of rRNA, which may cause cells involved in the development of facial bones and tissues to die early
  • This premature cell death may lead to the signs and symptoms of TCS. It is still unclear why the effects of these mutations are generally limited to facial development
• TCOF1 or POLR1D gene mutations are inherited in an autosomal dominant manner. On the other hand, POLR1C gene is inherited in an autosomal recessive manner

(Source: Treacher Collins Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Autosomal dominant pattern of inheritance: Autosomal dominant conditions are traits or disorders that are present when only one copy of the mutation is inherited on a non-sex chromosome. In these types of conditions, the individual has one normal copy and one mutant copy of the gene. The abnormal gene dominates, masking the effects of the correctly function gene. If an individual has an autosomal dominant condition, the chance of passing the abnormal gene on to their offspring is 50%. Children, who do not inherit the abnormal gene, will not develop the condition or pass it on to their offspring.

Autosomal recessive mode of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Treacher Collins Syndrome?

The signs and symptoms of Treacher Collins Syndrome may include:

Very frequently present symptoms in 80-99% of the cases:

• Downslanted palpebral fissures
• Hypoplasia of the maxilla
• Hypoplasia of the zygomatic bone
• Malar flattening
• Micrognathia
• Midface retrusion
• Open bite
• Retrognathia
• Short face
• Skeletal dysplasia

Frequently present symptoms in 30-79% of the cases:

• Absent eyelashes
• Cleft eyelid
• Conductive hearing impairment
• Frontal bossing
• Iris coloboma
• Low anterior hairline
• Microtia
• Narrow internal auditory canal
• Reduced number of teeth
• Visual impairment
• Wide nasal bridge

Occasionally present symptoms in 5-29% of the cases:

• Abnormality of dental enamel
• Abnormality of dental morphology
• Abnormality of the adrenal glands
• Abnormality of the vertebral column
• Blepharospasm
• Brachycephaly
• Branchial fistula
• Choanal atresia
• Cleft palate
• Cryptorchidism
• Dysphasia
• Encephalocele
• Failure to thrive
• Glossoptosis
• Hypertelorism
• Hypoplasia of penis
• Microphthalmia
• Multiple enchondromatosis
• Patent ductus arteriosus
• Preauricular skin tag
• Rectovaginal fistula
• Respiratory insufficiency
• Thyroid hypoplasia
• Tracheoesophageal fistula
• Wide mouth

In addition to the above, abnormality of bone mineral density may also exist in some affected individuals.

(Source: Treacher Collins Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Treacher Collins Syndrome Diagnosed?

Treacher Collins Syndrome is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Treacher Collins Syndrome?

The complications of Treacher Collins Syndrome may include:

• Problems with chewing food, due to abnormalities in the number and structure of teeth
• Severe hearing loss
• Development of cataracts
• Obstructive sleep apnea
• Low self-esteem due to one’s appearance
• Depression

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Treacher Collins Syndrome Treated?

• There is currently no cure for Treacher Collins Syndrome. Treatment is tailored to the specific needs of each affected person. Ideally, treatment is managed by a multidisciplinary team of craniofacial specialists
• Newborns may need special positioning or tracheostomy to manage the airway. Hearing loss may be treated with bone conduction amplification, speech therapy, and/or educational intervention
• In many cases, craniofacial reconstruction is needed. Surgery may be performed to repair cleft palate, to reconstruct the jaw, or to repair other bones in the skull. The specific surgical procedures used and the age when surgery is performed depends on the severity of the abnormalities, overall health and personal preference
• There are some possible treatments that are being investigated. Researchers are looking for ways to inhibit a protein called p53, which helps the body to kill off unwanted cells. In people with TCS, p53 is abnormally activated, leading to the loss of specific cells and ultimately causing features of TCS. It has been proposed that inhibiting the production of p53 (or blocking its activation) may help to treat affected people. However, more research is needed to determine if this type of treatment is effective and safe
• Researchers are also studying the use of stems cells found in fat tissue to be used alongside surgery in people with TCS and other craniofacial disorders. Early studies have shown that surgical outcomes may be improved using these stem cells to help stimulate the regrowth of affected areas. However, this therapy is still experimental and controversial

(Source: Treacher Collins Syndrome; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How can Treacher Collins Syndrome be Prevented?

Treacher Collins Syndrome may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Treacher Collins Syndrome? (Outcomes/Resolutions)

• The prognosis of Treacher Collins Syndrome is dependent upon the severity of the signs and symptoms and associated complications, if any
• Individuals with mild conditions have better prognosis than those with severe symptoms and complications
• Typically, the prognosis may be assessed on a case-by-case basis

Additional and Relevant Useful Information for Treacher Collins Syndrome:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/