Treacher Collins syndrome (TCS) is a congenital disorder that impacts the development of the bones and tissues in the face, a process that occurs during the early stages of pregnancy. This rare genetic condition is one of a group of disorders known as mandibulofacial dysostoses. TCS is characterized by distinctive, symmetrical facial differences, though the severity of these characteristics can vary widely among affected individuals. The condition occurs in approximately one in 50,000 live births globally, making it an uncommon diagnosis.
The Genetic Basis of Treacher Collins Syndrome
Treacher Collins syndrome arises from a genetic change that disrupts the formation of craniofacial structures during embryonic development. The gene most frequently implicated is TCOF1, which is responsible for up to 93% of all cases. Less commonly, mutations in the genes POLR1C and POLR1D have also been identified as causes of the syndrome.
The TCOF1 gene provides instructions for making a protein called treacle. Disruption of the treacle protein’s function impairs the generation and survival of neural crest cells, which are the precursor cells for the facial bone, cartilage, and connective tissues. The resulting deficiency in these cells leads to the underdevelopment of the facial skeleton that is characteristic of TCS.
The inheritance pattern for Treacher Collins syndrome is typically autosomal dominant for mutations in the TCOF1 and POLR1D genes, meaning only one copy of the altered gene in each cell is sufficient to cause the disorder. However, the condition often appears in individuals with no history of the disorder in their family, resulting from a spontaneous or de novo mutation. Approximately 60% of cases are due to these new mutations rather than being inherited from a parent.
Mutations in the POLR1C gene are associated with an autosomal recessive inheritance pattern, requiring a person to inherit an altered copy from both parents to be affected. The severity of the condition can vary greatly, even within the same family.
Defining Craniofacial Characteristics
The features of Treacher Collins syndrome result from the abnormal development of the first and second pharyngeal arches. These characteristics are typically symmetrical and vary in severity, involving the cheekbones, jaw, eyes, and ears.
Malar hypoplasia (underdevelopment of the cheekbones) is a hallmark of the syndrome, often giving the face a sunken appearance. The zygomatic arch and the lower border of the eye socket are frequently flattened or absent. This midface underdevelopment is often accompanied by micrognathia, a small lower jaw and chin.
The small jaw size can cause the chin to be recessed, a condition called retrognathia, and may lead to a poor alignment of the teeth. These mandibular issues can also create a high palate or, less commonly, a cleft palate. The eyes present with distinctive features, most notably a downward slant to the outer corners, known as downslanting palpebral fissures.
A common eye feature is a coloboma, or a notch, in the lower eyelid, which occurs in over half of affected individuals. Eyelashes are often sparse or completely absent on the outer third of the lower lid. These eyelid abnormalities can lead to dryness and an increased risk of eye infections.
External ear anomalies are also highly prevalent and include microtia (small, misshapen outer ears) or anotia (entirely absent ears). These external ear issues are frequently associated with atresia, the narrowing or complete absence of the ear canals. Most individuals experience conductive hearing loss, typically affecting both ears, because the tiny bones of the middle ear are often malformed or the ear canal is blocked.
These structural characteristics can lead to functional difficulties, particularly with breathing and feeding in infancy. The small jaw and chin can narrow the upper respiratory tract, sometimes causing life-threatening airway compromise. Feeding issues, especially in newborns, may arise due to the small jaw, cleft palate, or difficulty coordinating sucking and swallowing with breathing.
Navigating Medical and Surgical Management
The management of Treacher Collins syndrome requires a multidisciplinary approach that begins immediately after birth. The primary focus in newborns is stabilizing respiratory function, as a restricted airway poses the most immediate threat. Some infants may require specific positioning, such as lying on their stomach, to help ease breathing.
For infants with severe breathing difficulties, a tracheostomy may be necessary, which involves creating a surgical opening in the windpipe. Feeding issues are addressed concurrently, and some babies may temporarily require tube feeding, such as a gastrostomy tube, to ensure they receive adequate nutrition and calories.
Craniofacial surgery is a core component of treatment, often starting with procedures to improve bone structure and function. Mandibular distraction osteogenesis is a technique used to gradually lengthen the underdeveloped lower jaw by cutting the bone and slowly pulling the segments apart, allowing new bone to form in the gap. This procedure can help alleviate breathing problems and improve the profile of the jaw.
Reconstruction of the underdeveloped cheekbones and eye sockets, often using bone grafts, may be performed later in childhood, typically around five to ten years of age. Corrective jaw surgery, known as orthognathic surgery, is usually delayed until the teenage years when facial growth is largely complete to ensure the most stable long-term result. Surgeons may also perform ear reconstruction for microtia, typically starting when the child is school-aged, using either rib cartilage or a synthetic implant to create a more typical outer ear shape.
Addressing auditory issues focuses on improving the conductive hearing loss. Since the inner ear structures are usually unaffected, bone conduction hearing aids, such as a Bone Anchored Hearing Aid (BAHA), are highly effective at transmitting sound directly to the inner ear, bypassing the malformed middle or outer ear. Speech therapy is also routinely implemented, as structural issues like cleft palate or a small jaw can impact speech development.