Genetic aspects of congenital aniridia
Aniridia is a complex progressive congenital disorder affecting all structures of the eye. It is characterized by a total absence or partial hypoplasia of iris, fovea and optic nerve hypoplasia, nistagmus, and cornea opacity. It may be accompanied by cataracts, glaucoma and additional developmental defects of the brain, olfactory system and pancreas. Aniridia has an autosomal dominant inheritance with complete penetrance and variable expressiveness. Heterozygous mutations in the PAX6 gene are the cause of congenital aniridia. PAX6 is one of the key embryogenesis regulators, it is conserved in all bilateral-symmetrical animals. PAX6 coordinates and synchronies the coherent morphogenesis processes in cells of different origin, as well as forms the ability of future eye tissues to respond to inductive signals. Mutations in the gene lead to complex damage of all structures of the eye. There are more than 600 different known mutations in the PAX6 gene. About 72% of all mutations associated with aniridia result in premature stop codon. Microdeletions of chromosome region 11p13 are found in about a third of the detected genetic defects in aniridia. Although aniridia associated mutations are found in PAX6 in more than 95% of cases, complex aniridia phenotypes might overlap with clinical phenotypes caused by changes in other genes (e.g. FOXC1, PITX2, PITX3). Differential exclusion of WAGR syndrome, Axenfeld-Rieger syndrome, Peters anomality and other rarer syndromes (according to the OMIM database, 17 syndromes) is to be carried out. 85% of aniridia cases occur as an isolated malformation, in about 13% of cases aniridia is a part of the WAGR syndrome, and in 2-5% of cases - a part of rarer syndromes.