Treacher Collins Syndrome

Overview

Treacher Collins syndrome (TCS) is a rare genetic disorder characterized by craniofacial deformities resulting from abnormal development of the bones and tissues of the face. Also known as mandibulofacial dysostosis, the condition affects structures derived from the first and second pharyngeal arches during embryonic development. Individuals with TCS often present with distinctive facial features such as underdeveloped cheekbones, small jaws and chins (micrognathia), downward-slanting eyes, and malformed or absent ears. Despite the physical manifestations, most people with Treacher Collins syndrome have normal intelligence. The severity of the disorder can vary widely, even among members of the same family. Early medical intervention and multidisciplinary care are essential for managing functional challenges related to breathing, hearing, and feeding.

Causes

Treacher Collins syndrome is primarily caused by mutations in one of the following genes:

• TCOF1: The most common cause of TCS, accounting for approximately 80-90% of cases. This gene provides instructions for making a protein called treacle, which is essential for the development of craniofacial structures.

• POLR1C and POLR1D: These genes are involved in RNA polymerase function and ribosome biogenesis, which are crucial for cell growth and protein production during facial development.

The disorder follows an autosomal dominant inheritance pattern in most cases, meaning only one copy of the altered gene is sufficient to cause the condition. However, up to 60% of cases arise from new (de novo) mutations with no family history. In rarer instances, autosomal recessive inheritance is observed, particularly with POLR1C mutations.

Symptoms

The signs and symptoms of Treacher Collins syndrome can range from mild to severe and primarily affect the head and face. Common clinical features include:

• Facial bone abnormalities: Underdeveloped zygomatic bones (cheekbones), micrognathia (small lower jaw), and maxillary hypoplasia.

• Eyes: Downward-slanting palpebral fissures, notching of the lower eyelids (coloboma), and sparse or absent eyelashes on the lower lid.

• Ears: Malformed or absent external ears (microtia), ear canal atresia, and conductive hearing loss due to middle ear malformations.

• Mouth and airway: Cleft palate, high-arched palate, and respiratory difficulties due to jaw and airway abnormalities.

• Hearing impairment: Present in up to 50% of individuals, often due to structural defects in the middle ear.

Despite these craniofacial anomalies, most individuals with TCS have normal cognitive development and intelligence.

Diagnosis

Diagnosis of Treacher Collins syndrome is based on clinical evaluation, family history, imaging studies, and genetic testing. Diagnostic approaches include:

• Physical examination: Characteristic facial features such as downward-slanting eyes, micrognathia, and malformed ears provide initial diagnostic clues.

• Radiographic imaging: CT or MRI scans of the skull and facial bones help assess the extent of bony abnormalities, particularly in the jaw and middle ear.

• Hearing tests: Audiologic evaluation to assess the presence and degree of hearing loss.

• Genetic testing: Identification of mutations in the TCOF1, POLR1C, or POLR1D genes confirms the diagnosis and can aid in genetic counseling.

• Prenatal diagnosis: Available through chorionic villus sampling or amniocentesis if there is a known familial mutation.

Treatment

There is no cure for Treacher Collins syndrome, and treatment is focused on managing symptoms, improving function, and addressing cosmetic concerns. A multidisciplinary team approach is essential, and treatment plans may include:

• Surgical interventions:

  • Reconstructive facial surgery to correct jaw, cheekbone, and orbital abnormalities

  • Repair of cleft palate or other oral defects

  • Ear reconstruction or prosthetic ears for cosmetic and functional purposes

  • Tracheostomy in severe cases with airway obstruction

• Hearing management:

  • Use of bone-anchored hearing aids (BAHA) or cochlear implants for conductive hearing loss

  • Speech therapy and early auditory rehabilitation

• Orthodontic care: Dental treatment for malocclusion or missing teeth, often in coordination with surgical procedures.

• Psychological support: Counseling and support services to address self-esteem and social challenges related to facial appearance.

Prognosis

The long-term outlook for individuals with Treacher Collins syndrome varies depending on the severity of symptoms and the success of medical and surgical interventions. Key aspects of prognosis include:

• Life expectancy: Generally normal if respiratory issues are managed effectively, particularly in infancy and early childhood.

• Quality of life: Most individuals lead full lives with the aid of surgical, hearing, and speech interventions. Early and ongoing therapy significantly enhances functional and social outcomes.

• Reproductive risk: Individuals with TCS have a 50% chance of passing the condition to their offspring if the gene mutation is inherited in an autosomal dominant fashion.

With proper medical care, educational support, and social integration, individuals with Treacher Collins syndrome can achieve their full potential and enjoy a good quality of life.