Introduction

Treacher Collins syndrome(TCS), also known as mandibulofacial dysostosis and Franceschetti- Zwahlen-Klein-syndrome, is a type of craniofacial disorder, meaning that it mainly affects the skull and facial structures.¹ TCS is a rare, genetic disorder; its occurrence is 1 in 50,000 births, compared to more common craniofacial disorders like cleft lip and palate. TCS is an autosomal dominant disorder, meaning you only need one parent with the gene to inherit its symptoms. 

 The clinical diagnosis of the condition can be tricky as there are overlapping characteristic features between TCS, Nager, Miller and Goldenhar syndrome. More modern technologies, like genetic testing and novel craniofacial imaging techniques, make the diagnosis of TCS more accurate. This allows for the physician to carry out an accurate treatment plan to improve the quality of life whilst also educating the family.^2,3

Clinical evaluation for diagnosis

People with TCS have characteristic facial features that are often described as more bird-like. The most commonly affected parts of the face are the eyes (periorbital areas), ears, cheekbones (zygomatic bones), and mouth area (zygomatic arches). It is estimated that 81% of people with TCS have differences in the zygomatic bone, and 78% of people’s upper and lower jaw area is affected. Ocular anomalies make up 89% of TCS cases, whereby 69% present with defects in the lower eyelid. This likely can have an impact on the person’s vision (33% of the time) and quality of life. Cataract, obstructive sleep apnea, dental anomalies, and other related breathing problems are also commonly attributed.

Craniofacial features

1. Hypoplasia - underdeveloped facial bones (cheekbone and lower jaw)
2. Antimongoloid slant - downward slanted outer corner of the eye 
3. Malformed external ear, and sometimes the inner and middle ear are also affected, causing conductive hearing loss or a mild degree of deficit
4. Blind fistulas(connection) between the angle of the ear to the corners of the mouth
5. Atypical tongue-shaped hairline extending towards the cheeks
6. Vision loss, strabismus, congenital cataracts, and even occasional microphthalmia or anophthalmia

Oral and dental abnormalities

1. Macrostomia (widened mouth), high arched palate (cleft palate also seen)
2. Abnormal or malaligned teeth
3. Salivary gland pathologies can cause dryness of the mouth, which can eventually lead to caries.
4. Temporomandibular joint development can be affected, and cause ankylosis

Functional impairments

1. A small lower jaw can cause difficulty in breathing, whereby a tracheostomy is sometimes performed.
2. Decreased mouth opening and difficulty feeding may result in a nasogastric tube to be used at a young age 
3. Cardiac problems have been reported in rare cases
4. Speech difficulty can be common as a result of hearing problems alongside difficulty moving the mouth to articulate^1,3,4

Imaging studies

 Craniofacial imaging techniques can be used as a diagnostic aid alongside the physical clinical evaluation. The imaging modality consists mainly of X-ray, computed tomography(CT), ultrasonography(USG), and even MRI scans. 

Radiographic evaluation

A radiographic evaluation is possible with the help of a CT or even with an occipitomental radiograph. These types of scans help visualise more dense, hard tissue like bone. The most clinically important feature of TCS is an underdeveloped (hypoplasia) or totally absent (aplasia) of the malar zygomatic arch, which can be identified by a CT scan. Other abnormalities that can be interpreted by radiography are dental anomalies, and ear anomalies like the absence of ear ossicles with fusion of the malleus and incus rudiments, or partial absence of stapes or complete absence of middle ear space.

MRI evaluations 

MRI scans help visualise soft tissues and are usually used in TCS to evaluate the inner ear, and assess breathing, as the width of the airway and paranasal sinus space is often reduced in this condition, which can affect breathing.^1,6

Prenatal diagnostic tests are very useful in the early detection of TCS. USG with 3D imaging is very useful in detecting abnormal facial features. 

The genetic basis of TCS

The most common genes associated with TCS are TCOF1, POLR1D, and POLR1C. Our facial structures are formed as a result of branchial arches, pouches, and grooves; a defect in the first and second branchial arches causes a defect in TCS². DNA sequencing can be done with a sample of amniotic fluid (prenatal) or blood. Genetic testing is reliable and can help confirm the genetic basis of TCS.²

Differentiating craniofacial conditions 

There is some overlap of facial characteristics in many craniofacial conditions. The most common mix-up in diagnoses with TCS is Nager syndrome, Miller syndrome, and Goldenhar syndrome. Genetic testing can rule out these syndromes and give a confirmatory diagnosis.⁶

Nager syndrome has nearly identical features but with an additional limb abnormality.

Miller syndrome exhibits ectropion, postaxial limb abnormality, and has an additional cleft lip with or without cleft palate. 

Goldenhar syndrome shows facial asymmetry, with a flattened temporal, maxillary and malar bone, as well as cognitive defects, which do not occur in TCS. 

Treatment 

As TCD is an early developmental condition, it requires a holistic, multidisciplinary medical approach to treat the wide range of symptoms and complications someone with TCD may encounter. The treatment plan should start from the time of birth and should be based on the severity of the condition, as there may be a need for gastrostomy, tracheostomy or speech therapy. If there is a cleft palate, then appropriate measures to ensure feeding should be taken. Surgeries to improve breathing, hearing, and to bring the lower jaw forward, should be done as soon as possible to improve development and the quality of life. 

For example, some surgical treatment options are:

• Distraction osteogenesis to bring the mandible forward
• Orthognathic surgery for both upper and lower jaw
• Bone reconstruction
• Bone-assisted hearing aid placement
• Rhinoplasty
• Palatoplasty
• Orthodontic treatment for correcting the teeth

Treatments will therefore start from infancy and may continue into adulthood. An important, often overlooked treatment is psychological consultation as it can be hard for those with TCS to grow up without being made to feel out of place, they may struggle to embrace this part of their life and require encouragement and more support than others, which in turn will help break down the social stigma surrounding the condtion.^6,7

FAQs

Do TCS ndividuals have normal intelligence? 

Yes, most of the individuals have a normal intelligence and life expectancy

Does a TCS patient have a normal life expectancy? 

Yes, they do have a normal life expectancy, but the breathing problem should be tackled as early as possible.

Is the disease treatable?

It cannot be treated completely as it is a genetic problem. But proper management of the condition is possible by the multidisciplinary approach of the medical team.

Is it possible to have kids for an individual with TCS? 

Yes, but there is a 50% chance that they will transmit the gene defect to their children.

Summary

TCS is commonly an autosomal dominant disorder transmitted genetically,but it can also happen sporadically. It mainly affects the facial bones, especially the zygomatic bone and lower jaw, other symptoms include effects to the eye, ear, sinus, and irregular dentition. This in turn can cause difficulty in breathing, hearing, vision, feeding and speaking. Therefore prenatal genetic testing for pregnancy at risk of TCS is important for diagnosis and helpful for the parents and surgeons to plan ahead of time. Postnatally, clinical diagnosis vis physical characteristics is possible, additionally with the help of imaging modalities. The approach to treatment requires multidisciplinary medical care, as it involves many physicians.