The Inheritance of Treacher Collins Syndrome
How is Treacher Collins syndrome inherited from parent to child? Treacher Collins syndrome is a condition inherited from one or both parents. The gene that causes the disorder passes on to a child through a dominant process. This means that when a single parent with the gene produces an offspring with another person, there is a 50 percent chance of the child being born with Treacher Collins syndrome. Regardless of which parent possesses the gene, the child still has the same chance of being born with the condition.
In order for a person to pass the gene on to offspring, the individual must also suffer from the genetic disorder. Certain cases in which both parents are afflicted with Treacher Collins syndrome, there is a nearly 100 percent chance that the child will be born with the disease. Scientists have found, however, that occasionally there are instances in which the child will not posses the dominant gene from either parent and thereby not become afflicted with Treacher Collins syndrome.
Occasionally, mutations can occur in the Treacher Collins gene that does not come from hereditary means. Spontaneous mutations are responsible for roughly 60 percent of all cases of Treacher Collins syndrome. When this situation occurs to one child, there is a minimal chance of a second child being born with the same condition. According to a study conducted on mice, rats and hamsters, high doses of vitamin A administered to fetuses in the womb can result in effects similar to Treacher Collins syndrome. However, while these conditions appear to be the same, the actual genetics of the child do not contain the mutation that causes the disease.
What Gene is Affected?
How is Treacher Collins syndrome inherited through DNA? The gene that causes Treacher Collins syndrome is TCOF1, located on chromosome 5. Specifically, the gene can be identified on chromosome bands 5q31.3-33.3. According to a 1996 report by Dr. M.J. Dixon, clinical research has successfully identified 20 different mutations that occur within the gene leading to the genetic disorder. The vast majority of these mutations were either insertions or deletions.
Different physical features can occur from different mutations, however the scientific community has not been able to identify which mutation will cause which effects for the most part. One major exception this occurred in a study released in a 2004 issue of the American Journal of Medical Genetics. Dr. K. Horiuchi identified a de novo truncating mutation, one not caused by the parent, impacted exon 17 of the TCOF1 gene causing specific effects such as craniosynostosis, the premature fusing of sections of an infant’s skull and choanal atresia, a disorder in which the nasal passage is blocked by a bony or soft tissue.
Ultimately, the effects of Treacher Collins syndrome are caused by a failure of the fetus to properly develop during the first trimester. The mutations to the TCOF1 gene causes the protein that stimulates craniofacial development to prematurely terminate. Without this protein, the fetus fails to fully develop the features of the face and head, particularly the eyes, mouth, ears and facial bones.
“Treacher Collins Syndrome” eMedicine: https://emedicine.medscape.com/article/946143-overview
“Treacher Collins Syndrome” New York Times: https://health.nytimes.com/health/guides/disease/treacher-collins-syndrome/overview.html
Dominant Gene Process. (Supplied by the National Institutes of Health; Public Domain; https://upload.wikimedia.org/wikipedia/commons/e/e1/Autodominant.jpg)
This post is part of the series: The Genetics of Treacher Collins Syndrome
Treacher Collins syndrome, also known as Mandibulofacial Dysostosis, is caused by mutations in the TCOF1 gene. This gene impacts the treacle protein, which impacts the development of craniofacial features such as the ears, eyes, mouth and bone structure.