Introduction
Treacher-Collins syndrome (TCS) is also known as Franceschetti-Zwalen-Klein syndrome, mandibulofacial dysostosis, and Treacher-Collins-Franceschetti syndrome. It is a deformity of facial bones and tissues. TCS affects the development of facial bones and tissues, with symptoms ranging from barely noticeable to severe.
Most individuals with TCS have underdeveloped facial bones, especially the cheekbones, and a very small jaw and chin (micrognathia). Other possible symptoms include cleft palate, eye abnormalities, and hearing loss. Treacher-Collin syndrome occurs due to genetic changes. It also causes hearing loss and external ear abnormalities. However, brain abnormalities and behavioral issues are also caused by this syndrome. This article explains treacher-collins syndrome.
What Is Treacher Collins Syndrome?
Treacher-Collins syndrome (TCS) is also known as mandibulofacial dysostosis, is an inherited condition with autosomal dominant transmission, affecting 1 in 50,000 live births. Most cases result from a mutation in the TCOF1 gene on chromosome 5q31.3. This gene encodes a nucleolar phosphoprotein called Treacle, essential for developing the first and second branchial arches. The penetrance of these mutations (alterations in the genetic makeup) is complete, but their expressivity varies.
In cases where TCS is fully expressed, diagnosis can be made based on clinical features. Common symptoms include hypoplasia of facial bones, particularly the mandible and zygomatic complex, down-slanting palpebral fissures, lower eyelid coloboma, and cleft palate. Conductive hearing loss occurs in 50 percent of cases due to outer and middle ear malformations.
What Causes Treacher Collins Syndrome?
Treacher-Collins syndrome, or mandibulofacial dysostosis, is a hereditary condition affecting about one in 50,000 people. Mutations in the TCOF1, POLR1C, or POLR1D genes cause up to 95 percent of Treacher Collins cases. These genes produce proteins crucial for the prenatal development of facial bones and tissues. In cases where no mutation in these genes is found, the genetic cause remains unknown. Genetic changes in the TCOF1, POLR1C, or POLR1D genes can cause TCS. If the TCOF1 or POLR1D genes are involved, TCS follows an autosomal dominant inheritance pattern, though about 60 percent of these cases arise from new genetic changes rather than being inherited. When the POLR1C gene is responsible, TCS is inherited in an autosomal recessive manner. In some instances, the genetic cause remains unknown.
What Are the Symptoms of Treacher Collins Syndrome?
TCS symptoms and severity vary greatly among individuals, even within the same family. Some people may have mild symptoms and go undiagnosed. Others may have significant abnormalities and life-threatening respiratory complications. Not every afflicted person will exhibit every symptom listed.
The following are the major characteristic symptoms:
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TCS affects facial bones, ears, and soft tissues around the eyes.
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Individuals may have distinctive facial features and develop hearing and vision problems.
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Abnormalities are typically symmetric and present at birth (congenital).
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Airway issues, cleft palate, hearing loss, and jaw issues can all impact speech and language development.
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Typically, intelligence is unchanged; brain and behavioral abnormalities like microcephaly and cognitive delay can occur.
The following are the facial abnormalities:
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Infants with TCS often have underdeveloped (hypoplastic) or absent cheekbones, causing a flat or sunken facial appearance.
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The lower jaw (mandible) is incompletely developed, leading to a small chin and lower jaw (micrognathia).
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Specific structures anchoring the lower jawbone to muscles can be flat or absent.
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Throat underdevelopment (pharyngeal hypoplasia) can contribute to feeding and breathing difficulties in early infancy.
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Children may experience obstructive sleep apnea, and short interruptions of normal breathing during sleep.
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In severe cases, life-threatening respiratory difficulties may develop.
The patient also faces respiratory and feeding difficulties, such as:
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Narrowing or obstructing nasal airways (choanal stenosis or atresia) can contribute to respiratory or feeding issues.
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Some children may have "Pierre Robin sequence" features: severe micrognathia, a tongue displaced backward (glossoptosis), and possibly an incomplete roof of the mouth (cleft palate).
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Even if the palate fuses, it may remain high-arched, affecting feeding and respiration.
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Mouth and jaw malformations can lead to dental abnormalities such as underdeveloped teeth (hypoplastic), misaligned teeth (malocclusion), missing teeth (tooth agenesis), discolored enamel (enamel opacity), and improper eruption of upper teeth (maxillary molars).
What Are the Ear Manifestations of Treacher Collins Syndrome?
The following are the ear manifestations of Treacher Collins syndrome:
1. Hearing Loss:
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Individuals with TCS may develop conductive hearing loss due to issues with sound wave conduction through the middle ear.
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This usually results from abnormalities in the middle ear structures.
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Individuals may have malformed or absent ossicles (incus, malleus, and stapes), the three tiny bones that transmit sound waves in the middle ear.
2. External Ear Abnormalities:
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The structures of the external ears are frequently nonexistent, tiny, or deformed (microtia).
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There may be narrowing (stenosis) or blockage (atresia) of the external ear canals.
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Outer ears may appear crumpled or rotated.
3. Inner Ear:
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The inner ear is usually unaffected.
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However, malformations of the cochlea (the bony spiral organ in the inner ear) and the vestibular apparatus (structures that play a role in balance) have been reported.
4. Additional Symptoms:
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Small skin growths or pits in front of the external ear are known as preauricular tags.
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A non-normal channel that drains the ears into the nose and is closed on one end (called a blind fistula).
How Is Treacher Collins Syndrome Treated?
Treacher-Collins syndrome can impact various areas of the head and face, so treatment with a multidisciplinary team is most effective at a specialist center. This team typically includes craniofacial surgeons, neurosurgeons, ENT surgeons, audiologists, dentists, orthodontists, geneticists, speech and language therapists, and other specialists as needed.
The priority is stabilizing a child's breathing problems. Severe cases may require a tracheostomy, an artificial opening into the windpipe, to facilitate breathing. Less severe cases might only need nighttime breathing support. Feeding issues can be addressed with enteral feeding, such as a feeding tube or gastrostomy, to bypass the mouth and throat. Cleft palate repair, if needed, is usually performed in the first year.
The underdeveloped jaw often requires treatment as the child grows, such as bone grafts and jaw distraction. Although this is a long-term treatment, it generally yields good results. Cheekbones might also need reconstruction using bone grafts or implants.
Ear reconstruction can be done later in childhood, creating a new ear modeled on the existing ear or, if both are not present, the parents' ears. While this improves appearance, it does not enhance function. Children with hearing impairments will need hearing aids, cochlear implants, and speech and language therapy.
Further surgeries may be necessary during childhood and adolescence for minor facial shape corrections. Final repairs are typically finished between the ages of 16 and 20.
Conclusion
Researchers are exploring new ways to treat Treacher Collins syndrome, which can inhibit its progression. More research is needed to determine its effectiveness and long-term safety. Some studies suggest that antioxidant supplements can protect or prevent facial deformities.
