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Treacher Collins syndrome (TCS) is a genetic disorder characterized by deformities of the ears, eyes, cheekbones, and chin. The degree to which a person is affected, however, may vary from mild to severe. Complications may include breathing problems, problems seeing, cleft palate, and hearing loss. Those affected generally have normal intelligence. TCS is usually autosomal dominant. More than half the time it occurs as a result of a new mutation rather than being inherited. The involved genes may include TCOF1, POLR1C, or POLR1D. Diagnosis is generally suspected based on symptoms and X-rays, and potentially confirmation by genetic testing. Treacher Collins syndrome is not curable. Symptoms may be managed with reconstructive surgery, hearing aids, speech therapy, and other assistive devices. Life expectancy is generally normal. TCS occurs in about one in 50,000 people. The syndrome is named after Edward Treacher Collins, an English surgeon and ophthalmologist, who described its essential traits in 1900. Signs and symptoms Symptoms in people with Treacher Collins syndrome vary. Some individuals are so mildly affected that they remain undiagnosed, while others have moderate to severe facial involvement and life-threatening airway compromise. Most of the features of TCS are symmetrical and are already recognizable at birth. The most common symptom of Treacher Collins syndrome is underdevelopment of the lower jaw and underdevelopment of the zygomatic bone. This can be accompanied by the tongue being retracted. The small mandible can result in a poor occlusion of the teeth or in more severe cases, trouble breathing or swallowing. The respiratory system of a child with Treacher Collins syndrome is the primary concern at birth, with other issues only addressed once respiratory function has been stabilized. Underdevelopment of the zygomatic bone gives the cheeks a sunken appearance. The external ear is sometimes small, rotated, malformed, or absent entirely in people with TCS. Symmetric, bilateral narrowing or absence of the external ear canal, is also described. In most cases, the bones of the middle ear and the middle ear cavity are misshapen. Inner ear malformations are rarely described. As a result of these abnormalities, a majority of the individuals with TCS have conductive hearing loss. Most affected people also experience eye problems, including coloboma (notches) in the lower eyelids, partial or complete absence of eyelashes on the lower lid, downward angled eyelids, drooping of upper and lower eyelids, and narrowing of the tear ducts. Vision loss can occur and is associated with strabismus, refractive errors, and anisometropia. It can also be caused by severely dry eyes, a consequence of lower eyelid abnormalities and frequent eye infections. Although an abnormally shaped skull is not distinctive for Treacher Collins syndrome, brachycephaly with bitemporal narrowing is sometimes observed. Cleft palate is also common. Dental anomalies are seen in 60% of affected people, including tooth agenesis (33%), discoloration (enamel opacities) (20%), malplacement of the maxillary first molars (13%), and wide spacing of the teeth. In some cases, dental anomalies in combination with mandible hypoplasia result in a malocclusion. This can lead to problems with food intake and the ability to close the mouth. Less common features of TCS may add to an affected person's breathing problems, including sleep apnea. Choanal atresia or stenosis is a narrowing or absence of the choanae, the internal opening of the nasal passages, which may also be observed. Underdevelopment of the pharynx can also narrow the airway. Features related to TCS that are seen less frequently include nasal deformities, high-arched palate, macrostomia, preauricular hair displacement, cleft palate, hypertelorism, notched upper eyelid, and congenital heart defects. Although facial deformity is often associated with developmental delay and intellectual disability, more than 95% of people affected with TCS have normal intelligence. The psychological and social problems associated with facial deformity can affect quality of life in individuals with TCS. Genetics Mutations in TCOF1, POLR1C, or POLR1D genes can cause Treacher Collins syndrome. TCOF1 gene mutations are the most common cause of the disorder, with POLR1C and POLR1D gene mutations causing an additional 2% of cases. In individuals without an identified mutation in one of these genes, the genetic cause of the condition is unknown. The TCOF1, POLR1C, and POLR1D genes code for proteins which play important roles in the early development of bones and other tissues of the face. Mutations in these genes reduce the production of rRNA, which may trigger the self-destruction (apoptosis) of certain cells involved in the development of facial bones and tissues. It is unclear why the effects of a reduction in rRNA are limited to facial development. Mutations in TCOF1 and POLR1D cause the autosomal dominant form of Treacher Collins, and mutations in POLR1C cause the autosomal recessive form. TCOF1 TCOF1 is the primary gene associated with TCS, a mutation in this gene being found in 90–95% of the individuals with TCS. However, in some individuals with typical symptoms of TCS, mutations in TCOF1 have not been found. Investigation of the DNA has resulted in the identification of the kind of mutations found in TCOF1. The majority of mutations are small deletions or insertions, though splice site and missense mutations also have been identified. Mutation analysis has unveiled more than 100 disease-causing mutations in TCOF1, which are mostly family-specific mutations. The only recurrent mutation accounts for about 17% of the cases. TCOF1 is found on the 5th chromosome in the 5q32 region. It codes for a relatively simple nucleolar protein called treacle, that is thought to be involved in ribosome assembly. Mutations in TCOF1 lead to haploinsufficiency of the treacle protein. Haploinsufficiency occurs when a diploid organism has only one functional copy of a gene, because the other copy is inactivated by a mutation. The one normal copy of the gene does not produce enough protein, causing disease. Haploinsufficiency of the treacle protein leads to a depletion of the neural crest cell precursor, which leads to a reduced number of crest cells migrating to the first and second pharyngeal arches. These cells play an important role in the development of the craniofacial appearance, and loss of one copy of treacle affects the cells' ability to form the bones and tissues of the face. Other mutations POLR1C and POLR1D mutations are responsible for a minority of cases of Treacher Collins. POLR1C is found on chromosome 6 at position 6q21.2 and POLR1D is found on chromosome 13 at position 13q12.2. Those genes code for a protein subunits shared between RNA polymerase I and III. Both of these polymerases are important for ribosome biogenesis. Diagnosis Genetic counseling TCS is inheri.... Discover the Jono Lancaster popular books. Find the top 100 most popular Jono Lancaster books.