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.
ERT has been shown to lead to better outcomes in MPS II patients. Gene editing therapy
In February 2019, medical scientists working with Sangamo Therapeutics, headquartered in Richmond, California, announced the first  "in body" human gene editing therapy to permanently alter DNA - in a patient with MPS II. Clinical trials by Sangamo involving gene editing using zinc finger nuclease  are ongoing as of February 2019. Prognosis
Earlier onset of symptoms is linked to a worse prognosis. For children who exhibit symptoms between the ages of 2 and 4, death usually occurs by the age of 15 to 20 years. The cause of death is usually due to neurological complications, obstructive airway disease, and cardiac failure. If patients have minimal neurologic involvement, they may survive into their 50s or beyond. Epidemiology
An estimated 2,000 people have MPS II worldwide, 500 of whom live in the United States.A study in the United Kingdom indicated an incidence among males around one in 130,000 male live births. History
The syndrome is named after physician Charles A. Hunter (1873–1955), who first described it in 1917. Research
Beginning in 2010, a phase I/II clinical trial evaluated intrathecal injections of a more concentrated dose of idursulfase than the intravenous formulation used in enzyme replacement therapy infusions, in hopes of preventing the cognitive decline associated with the severe form of the condition. Results were reported in October 2013.