Treacher Collins syndrome is a condition that affects the development of bones and other tissues of the face. The signs and symptoms of this disorder vary greatly, ranging from almost unnoticeable to severe. Most affected individuals have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.

People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called an eyelid coloboma. Some affected individuals have additional eye abnormalities that can lead to vision loss. This condition is also characterized by absent, small, or unusually formed ears. Hearing loss occurs in about half of all affected individuals; hearing loss is caused by defects of the three small bones in the middle ear, which transmit sound, or by underdevelopment of the ear canal. People with Treacher Collins syndrome usually have normal intelligence.

Variants (also known as mutations) in the TCOF1, POLR1C, or POLR1D gene can cause Treacher Collins syndrome. TCOF1 gene variants are the most common cause of the disorder, accounting for 81 to 93 percent of all cases. POLR1C and POLR1D gene variants cause an additional 2 percent of cases. In individuals without an identified variant in one of these genes, the genetic cause of the condition is unknown.

The proteins produced from the TCOF1, POLR1C, and POLR1D genes all appear to play important roles in the early development of bones and other tissues of the face. These proteins are involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into new proteins, which is essential for the normal functioning and survival of cells.

Variants in the TCOF1, POLR1C, or POLR1D gene reduce the production of rRNA. Researchers speculate that a decrease in the amount of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. The abnormal cell death could lead to the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Normal Function

The POLR1C gene provides instructions for making one part (subunit) of two related enzymes called RNA polymerase I and RNA polymerase III. These enzymes are involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. Both enzymes help synthesize a form of RNA known as ribosomal RNA (rRNA). RNA polymerase III also plays a role in the synthesis of several other forms of RNA, including transfer RNA (tRNA). Ribosomal RNA and transfer RNA assemble protein building blocks (amino acids) into functioning proteins, which is essential for the normal functioning and survival of cells.

Based on its involvement in Treacher Collins syndrome, the POLR1C gene appears to play a critical role in the early development of structures that become bones and other tissues of the face.

Health Conditions Related to Genetic Changes

Treacher Collins syndrome

At least six mutations in the POLR1C gene have been identified in people with Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. These mutations appear to alter the structure and function of the POLR1C protein, which reduces the amount of functional RNA polymerase I and RNA polymerase III in cells. Consequently, less rRNA is produced. Researchers speculate that a shortage of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the early development of facial bones and tissues. The abnormal cell death could underlie the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Coloboma

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Other Names for This Gene

• AC40
• DNA-directed RNA polymerase I subunit C
• DNA-directed RNA polymerases I and III 40 kDa polypeptide
• DNA-directed RNA polymerases I and III subunit RPAC1
• polymerase (RNA) I polypeptide C
• polymerase (RNA) I polypeptide C, 30kDa
• polymerase (RNA) I subunit C
• RNA polymerase I subunit C
• RNA polymerases I and III subunit AC1
• RPA39
• RPA40
• RPA5
• RPAC1
• RPAC1_HUMAN
• RPC40

Genomic Location

Normal Function

The POLR1D gene provides instructions for making one part (subunit) of two related enzymes called RNA polymerase I and RNA polymerase III. These enzymes are involved in the production (synthesis) of ribonucleic acid (RNA), a chemical cousin of DNA. Both enzymes help synthesize a form of RNA known as ribosomal RNA (rRNA). RNA polymerase III also plays a role in the synthesis of several other forms of RNA, including transfer RNA (tRNA). Ribosomal RNA and transfer RNA assemble protein building blocks (amino acids) into functioning proteins, which is essential for the normal functioning and survival of cells.

Based on its involvement in Treacher Collins syndrome, the POLR1D gene appears to play a critical role in the early development of structures that become bones and other tissues of the face.

Health Conditions Related to Genetic Changes

Treacher Collins syndrome

At least 20 mutations in the POLR1D gene have been identified in people with Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. These mutations appear to alter the structure and function of the POLR1D protein, which reduces the amount of functional RNA polymerase I and RNA polymerase III in cells. Consequently, less rRNA is produced. Researchers speculate that a shortage of rRNA may trigger the self-destruction (apoptosis) of certain cells involved in the early development of facial bones and tissues. The abnormal cell death could underlie the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Coloboma

MedlinePlus Genetics provides information about Coloboma

Other Names for This Gene

• AC19
• DNA-directed RNA polymerase I subunit D
• DNA-directed RNA polymerases I and III subunit RPAC2
• FLJ20616
• MGC9850
• polymerase (RNA) I polypeptide D
• polymerase (RNA) I polypeptide D, 16kDa
• polymerase (RNA) I subunit D
• RNA polymerase I subunit D
• RNA polymerases I and III subunit AC2
• RPA16
• RPA9
• RPAC2
• RPAC2_HUMAN
• RPC16
• RPO1-3

Genomic Location

Normal Function

The TCOF1 gene provides instructions for making a protein called treacle. This protein is active during early embryonic development in structures that become bones and other tissues of the face, and it appears to play a critical role in the formation of these structures.

Studies suggest that treacle is involved in the production of a molecule called ribosomal RNA (rRNA), a chemical cousin of DNA. Ribosomal RNA helps assemble protein building blocks (amino acids) into functioning proteins, which is essential for the normal functioning and survival of cells. Treacle is active in the nucleolus, which is a small region inside the nucleus where rRNA is produced.

Health Conditions Related to Genetic Changes

Treacher Collins syndrome

About 200 mutations in the TCOF1 gene have been identified in people with Treacher Collins syndrome, a condition that affects the development of bones and other tissues of the face. Most of these mutations insert or delete a small number of DNA building blocks (base pairs) in the TCOF1 gene, which leads to a reduction in the amount of functional treacle in cells. As a result, the production of rRNA is reduced, which likely triggers the self-destruction (apoptosis) of certain cells involved in the early development of facial bones and tissues. Researchers believe that this abnormal cell death may lead to the specific problems with facial development found in Treacher Collins syndrome. However, it is unclear why the effects of a reduction in rRNA are limited to facial development.

Coloboma

MedlinePlus Genetics provides information about Coloboma

Other Names for This Gene

• TCOF_HUMAN
• TCS
• Treacher Collins syndrome protein
• Treacher Collins-Franceschetti syndrome 1
• treacle

Genomic Location

When Treacher Collins syndrome results from variants in the TCOF1 or POLR1D gene, it is considered an autosomal dominant condition, which means one copy of the altered gene in each cell is sufficient to cause the disorder. About 60 percent of these cases result from new variants in the gene and occur in people with no history of the disorder in their family. In the remaining autosomal dominant cases, a person with Treacher Collins syndrome inherits the altered gene from an affected parent.

When Treacher Collins syndrome is caused by variants in the POLR1C gene, the condition has an autosomal recessive pattern of inheritance. Autosomal recessive inheritance means both copies of the gene in each cell have variants. The parents of an individual with an autosomal recessive condition each carry one copy of the altered gene, but they typically do not show signs and symptoms of the condition.

The signs and symptoms of Treacher Collins syndrome vary greatly, ranging from almost unnoticeable to severe. Most affected people have underdeveloped facial bones, particularly the cheek bones, and a very small jaw and chin (micrognathia). Some people with this condition are also born with an opening in the roof of the mouth called a cleft palate. In severe cases, underdevelopment of the facial bones may restrict an affected infant's airway, causing potentially life-threatening respiratory problems.

People with Treacher Collins syndrome often have eyes that slant downward, sparse eyelashes, and a notch in the lower eyelids called a coloboma. Some people have additional eye abnormalities that can lead to vision loss. The condition is also characterized by absent, small, or unusually formed ears. Defects in the middle ear (which contains three small bones that transmit sound) cause hearing loss in about half of affected people. People with Treacher Collins syndrome usually have normal intelligence.