The TCOF1 gene is located on chromosome 5, at position 5q32-q33.1. This gene contains the instructions for producing a protein known as treacle. Treacle is a nucleolar phosphoprotein, found within the nucleolus, a specialized region inside the cell’s nucleus.
What TCOF1 Does
The treacle protein plays a role in early embryonic development, specifically in the formation of facial bones and tissues. This protein is involved in ribosome biogenesis, the process cells use to create ribosomes. Ribosomes are cellular machinery responsible for assembling proteins from amino acid building blocks, which is vital for cell function.
Treacle contributes to ribosome biogenesis by promoting the transcription of ribosomal DNA (rDNA) genes and assisting in the modification of pre-ribosomal RNA (pre-rRNA). It interacts with other proteins, such as upstream binding factor (UBF) and NOP56, to ensure proper rRNA production and processing. While its precise function in facial development is not fully understood, its involvement in producing ribosomal RNA suggests a role in the development of embryonic cells that form facial structures.
Understanding Treacher Collins Syndrome
Mutations in the TCOF1 gene are the most frequent cause of Treacher Collins Syndrome (TCS). TCS is a genetic disorder characterized by abnormalities in the development of facial bones and tissues. The severity of these features can vary significantly among individuals, ranging from barely noticeable to severe.
Common physical characteristics of TCS include:
Underdeveloped facial bones, particularly flattened cheekbones, and a small jaw and chin (micrognathia).
Downward-sloping eyes, an eyelid coloboma, and sometimes sparse or absent lower eyelashes.
Ear abnormalities, such as absent, small, or unusually formed ears (microtia or atresia), which can lead to conductive hearing loss in about half of affected individuals.
A cleft palate.
An overgrowth of scalp hair extending onto the cheeks.
TCS is inherited in an autosomal dominant manner, meaning only one copy of the altered TCOF1 gene is sufficient to cause the condition. In about half of all cases, the TCOF1 gene mutation occurs spontaneously at conception, without a family history of the disorder. While TCOF1 is the primary gene associated with TCS, mutations in other genes, such as POLR1C and POLR1D, can also cause similar conditions.
Diagnosing and Managing the Condition
Diagnosing Treacher Collins Syndrome can occur both before and after birth. Prenatal diagnosis may be suspected during routine ultrasound examinations, particularly in the second or third trimester, if characteristic facial anomalies like micrognathia, malar hypoplasia, and ear malformations are observed. Three-dimensional ultrasound can be especially useful for visualizing these facial differences, though definitive diagnosis requires genetic testing to identify mutations in the TCOF1 gene. Postnatal diagnosis is made based on a physical examination of the infant, noting the distinctive facial features, followed by genetic testing to confirm the presence of a gene mutation.
Managing Treacher Collins Syndrome requires a comprehensive and multidisciplinary approach due to the complex nature of the condition. A team of specialists, including craniofacial surgeons, otolaryngologists, audiologists, speech therapists, and nutritionists, collaborate to address the various physical and functional challenges. Surgical interventions, such as jaw distraction to lengthen the mandible or reconstruction of cheekbones, are often performed in stages throughout childhood and adolescence to improve facial structure and function. Hearing loss, a common issue, is managed with hearing aids or bone-anchored hearing systems (BAHA) to promote communication development. Speech therapy is frequently necessary, especially if a cleft palate or hearing impairment affects speech development. In severe cases, particularly with significant breathing difficulties due to a small jaw, a tracheostomy may be required to secure the airway.
Early intervention and ongoing supportive care are important to optimize outcomes and support the individual’s development.