Treacher Collins 1, 2 and 3, ... Syndrome (Treacher Collins Franceschetti-syndrome ..., Franceschetti-Zwahlen-Klein syndrome ..., mandibulofacial dysostosis -MFD1-; Dysplasia cigoauromandibular) (Treacher Collins syndrome) - Genes TCOF1 , POLR1C or POLR1D.

Treacher Collins syndrome is a group of disorders that affect bone and other facial tissues, caused during development. This syndrome varies widely in its manifestations, may be negligible or have very significant varied manifestations. Most of those affected have limited development of some facial bones, with mandibular hypoplasia, hypoplastic zygomatic arches, micrognathia, and some have cleft palate. In the most severe cases can be affected even the upper airways. Often they have other disorders such as impaired ocular arrangement, coloboma lower eyelids, disorders of the pinnae (absence, reduced size, or morphological alteration), atresia of the external ear canal, involvement of the middle ear with hearing loss, or eye disorders involving loss of vision.

This syndrome is caused, in most cases, by mutation of the gene TCOF1 (Treacher Collins Franceschetti Syndrome-1), located on the long arm of chromosome 5 (5q32-q33.1). The gene encodes a protein involved in bone development and other facial tissues prenatally. They described 200 mutations in this gene, which in most cases correspond to small insertions or deletions. However, other variants of this syndrome in which mutations lie in other genes: Treacher Collins syndrome with 2 mutations in the gene POLR1D and Treacher Collins syndrome with three mutations in the gene POLR1C.

The POLR1D genes located on the long arm of chromosome 13 (13q12.2) and POLR1C gene, located on the short arm of chromosome 6 (6p21.1), encoding a subunit of RNA polymerase I enzymes and RNA polymerase III . These enzymes are involved in the synthesis of ribonucleic acid (RNA), ribosomal RNA helping synthesize (rRNA) and transfer RNA (tRNA), which is essential for the normal function and survival of the cells. The POLR1D gene appears to play a critical role in the initial development of structures that become bones and other tissues of the face. They described a 20 mutations in the POLR1D gene and at least 6 mutations in the POLR1C gene, altering the structure and function of the protein, reducing the amount of RNA polymerase I and RNA polymerase III functional in the cells produced by Consequently, less rRNA. It is believed that the decrease in rRNA can trigger apoptosis of certain cells involved in early development of bones and facial tissues.

When the Treacher Collins syndrome results from mutations in the gene TCOF1 or POLR1D, is considered an autosomal dominant disorder, which means that a copy of the altered gene in each cell is sufficient to cause disease. About 60% of these cases result from new mutations in the gene and occur in people with no history of disease in your family. In cases of autosomal dominant transmission remaining, a person with the syndrome inherited the altered gene from an affected parent. When the alteration is caused by mutations in the gene POLR1C syndrome it has an autosomal recessive inheritance pattern, which means that both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.  

Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Treacher Collins syndrome, by complete PCR amplification of all exons of TCFO1, POLR1C or POLR1D, respectively, and subsequent sequencing genes.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).