Tricher-Collins syndrome affects the development of bone and other facial tissues. The signs and symptoms of this disorder can vary significantly, from almost imperceptible to severe. Most victims have undeveloped facial bones, in particular cheekbones, and a very small jaw and chin (in newborns). Some people with Tricher-Colins syndrome are born with a hole in their mouth called the "cleft palate." In severe cases, underdevelopment of the facial bones can limit the victim's airways, causing potentially life-threatening diseases.
Often people with this disease have their eyes tilted down, rare eyelashes, and there is a defect in the lower eyelids called
coloboma. This causes additional ophthalmic disorders that can lead to vision loss. In addition, small or unusually shaped ears or their absence are possible.
Hearing loss occurs in about half the cases. It is caused by defects in three small bones of the middle ear that transmit sound, or by the underdevelopment of the ear canal. The presence of Tricher-Collins syndrome does not affect the intellect: as a rule, it is normal.
Which gene mutations cause Tricher-Collins syndrome?
The most common cause: mutations in the TCOF1, POLR1C, or POLR1D genes.
The TCOF1
gene mutation is the cause of 81-93% of all cases. POLR1C and POLR1D - an additional 2% of cases. In individuals without a specific mutation of one of the genes, the cause of the disease is unknown.
The TCOF1, POLR1C, and POLR1D genes play an important role in the onset of bone and other facial tissue development. They are involved in the production of a molecule called ribosomal RNA (rRNA), the chemical cousin of DNA. Ribosomal RNA helps to assemble blocks of proteins (amino acids) into new proteins, which are necessary for the normal functioning and survival of cells. Mutations in the TCOF1, POLR1C, or POLR1D genes reduce rRNA production. Researchers believe that reducing the amount of rRNA can lead to the self-destruction of certain cells involved in the development of facial bones and tissues. Abnormal cell death can lead to certain problems with facial development in people with Tricher-Collins syndrome.
How is Tricher-Collins syndrome inherited?
If the disease occurs due to a mutation in the TCOF1 or POLR1D genes, it is considered that this is an autosomal dominant disease. About 60% of cases of the disease appear as a result of new mutations in the gene and occur in people without a history in the family. In other cases, the syndrome is inherited through the altered gene from the parents.
When a disease is caused by mutations in the POLR1C gene, it is considered to be an autosomal recessive type of inheritance. Parents of an individual with an autosomal recessive disease have one copy of the mutated genes, but they usually do not show signs and symptoms of the disease.
Syndrome treatment
Treatment depends on the severity of the condition, but may include:
- genetic counseling - for an individual or the whole family, depending on whether the disease is hereditary or not;
- hearing aids - in the case of conductive hearing loss;
- dental treatment, including orthodontic, aimed at correcting a malocclusion;
- speech therapy classes to improve communication skills. Defectologists also work with people who have trouble swallowing food or drinks;
- surgical methods to help improve the appearance and quality of life.