Treacher Collins Syndrome

What is a Treacher Collins Syndrome?

Treacher Collins syndrome (TCS) or mandibulofacial dysostosis is a rare congenital disorder characterized by serious facial dysmorphias and is found in 1 out of 50.000 live births in Europe. Edward Richard Collins was a famous English surgeon and ophthalmologist who made the first steps in studying TCS in early 19th century.

There is a wide range clinical presentation of the syndrome that goes from unnoticed to life threatening. In most cases it presents with ophthalmological defects(amblyopia, strabismus, vision loss) along with downward-slanting eyes, sparse eyelashes and eyelid coloboma(notches).

The outer ears may vary from aplastic to deformed and the underdevelopment of the three middle ear bones and Eustachian canal causes conductivity hearing loss in every second patient. Other usual deformities include micrognathia, cleft palate and hypoplastic zygomatics, hypertelorism, choanal atresia, nasal deformities, preauricular hair displacement etc.

In the worst case scenario, infants with the syndrome may present with respiratory failure due to serious airway architecture deformity. However, in most cases children enter adulthood with normal intelligence and life expectancy.

Inheritance Patterns

Until today three genes have been linked to TCS: TCOF1, POLR1C, and POLR1D. TCOF1 is responsible for at least 8 out of 10 cases, while in some case none of the above is detected. POLR1D has the smallest incidence, because, unlike the rest, it is inherited in the autosomal recessive pattern, meaning that each parent must carry and give one pathologic gene to the child without, however, having any clinical signs of the syndrome.

TCOF1 and POLR1C appear as a new de novo mutation in 60% of the case and the rest 40% is inherited by the autosomal dominant pattern, meaning that one parent with one gene, and simultaneously, the phenotype of the disease is enough to give birth to a child with the syndrome.

Genetic Background

All three genes code the production of rRNA(ribosomal), which is crucial in DNA translation and protein production, and is why TCS is considered a ribosopathy. The genetic alteration, usually a deletion or an insertion, results in lower rRNA production, which in recent studies was directly linked to apoptosis.

Even more interesting is how the damaged cells are so specifically chosen in space and time, since the genetic change only affects those that are part of the facial bone or soft tissue exclusively during fetal life. It is found that treacle the protein coded by TCOF1 is active only in embryonic environment. What is still a mystery is why only facial structures are influenced and would be an interesting field of further study.

Diagnosis

Prenatal diagnosis can be achieved through ultrasonography and gene detection with chorionic villus sampling or amniocentesis from the early stages of pregnancy. However sometimes mild clinical presentation raises no suspicion and passes unnoticed until birth or in some extreme cases even until early life.

In order to clinically differentiate TCS from other entities with similar presentation such as acrofacial dysostoses, Nager syndrome, Miller syndrome, hemifacial macrosomia and Goldenhar syndrome OMNES score was designed. OMNES is both an acronym standing for TCS’ most frequent features: Orbital asymmetry, Mandible, facial Nerve Ear, Soft tissue, and a score giving 0-3 points in the above features, 0 if they appear totally normal and 3 if they have the severest deformity.

The score’s sum ranges from 0 to 15,with score above 12 setting the definite diagnosis and above 3-4 expressing the need for further genetic investigation. Last but not least radiological results such as a panoramic dental as well other x-rays of the head, along with a CT scan provide further information for diagnosis, staging and, most importantly, intervention management. Experienced clinicians, or those familiar with syndrome’s characteristic face may set the diagnosis at first sight.

Treatment

Children with TCS need special care from a group of professional from several disciplines, surgeons, psychologists, special educator atc. Treatment takes part in three chronological steps. In the first two years of life, the maintenance of open and stable feeding and breathing ways is of highest importance and may sometimes require a tracheostomy or gastrostomy.

Next, once the above are secured, and until early puberty, we have to investigate the presence and manage the treatment of hearing loss through bone conduction amplification and speech therapy, so that the child can have a normal speech and social behavior development.

Finally, until the child reaches adolescence all orthognathic surgeries should have been completed. It is obvious that treatment is a life-long procedure and needs lots of psychological endurance and familiarization with hospitals not only from the part of the child, but also from the whole family.

Closure

We have to stretch that genetics have only an estimated effect on our lives and in order for one to blossom the proper environment is needed. Taking that into account, a child born with Treacher Collins Syndrome may have the luck to enjoy a thorough treatment and live a normal life making his dreams come true, whereas another child, born with the same problem, in a place with more poverty, lower education, or in the absence of a healthcare system, it may not even have the chance to listen and talk, or even worse breathe, and thus live.

It is important to keep in mind that environment and society can radically influence what is written in our genes, and this is an ultimate privilege of our era that is always growing.

References:

1. Treacher Collins Syndrome – Sara Huston Katsanis, MS and Ethylin Wang Jabs, MD. Initial Posting: July 20, 2004; Pagon RA, Adam MP, Ardinger HH, et al., editors. Seattle (WA): University of Washington, Seattle; 1993-2017.Argenta LC, Iacobucci JJ. Treacher Collins syndrome: present concepts of the disorder and their surgical correction. World J Surg. 1989;13:401–9.
2. Trainor PA, Dixon J, Dixon MJ. Treacher Collins syndrome: etiology, pathogenesis and prevention. Eur J Hum Genet. 2009 Mar;17(3):275-83. doi: 10.1038/ejhg.2008.221. Epub 2008 Dec 24
3. Vento AR, et al., The O.M.E.N.S classification of hemifacial microsomia, 1991, Cleft Palate Craniofac, J 28,p. 68-76
4. Wieczorek D, Gener B, González MJ, Seland S, Fischer S, Hehr U, Kuechler A, Hoefsloot LH, de Leeuw N, Gillessen-Kaesbach G, Lohmann DR. Microcephaly, microtia, preauricular tags, choanal atresia and developmental delay in three unrelated patients: a mandibulofacial dysostosis distinct from Treacher Collins syndrome. Am J Med Genet. 2009;149A:837–43.