Aniridia is a developmental anomaly of the entire eye, characterized by varying degrees of iris hypoplasia. Ocular abnormalities associated with aniridia include persistent papillary membrane, congenital cataracts, ectopia lentis, developmental glaucoma, corneal pannus with progressive keratopathy and foveal hypoplasia. The most severe presentation of aniridia is complete absence of the iris. Milder disease may include enlargement and irregularity of the pupil and small, slit-like defects in the anterior layer. Vision is variably affected, and the severity of vision loss tends to correlate with the presence of other associated ocular defects. Approximately 70% of the cases with isolated aniridia (i.e. aniridia without associated anomalies) are familial while the remaining 30% of cases are sporadic. Aniridia may be caused by heterozygous mutations in the PAX6 gene. PAX6 mutations have also been described in a host of other ocular developmental abnormalities that appear clinically distinct from aniridia, including: microphthalmia with or without coloboma; Axenfeld Rieger syndrome, optic nerve hypoplasia and other congenital optic nerve anomalies; and a specific form of corneal dystrophy. Aniridia may also be seen as part of the WAGR (Wilms tumor, aniridia, genital anomalies and mental retardation) syndrome, which is caused by a deletion of chromosome 11p13, the genomic region harboring both the PAX6 and WT1 genes. Some cases of sporadic aniridia involve de novo submicroscopic deletions in this chromosomal region and therefore could place the patient at risk for developing Wilms tumor. Large gross chromosomal deletion can be detected by cytogenetic analysis, fluorescent in situ hybridization (FISH) and oligo array Comparative Genomic Hybridization (oligo aCGH) analysis. However these methods will not detect partial PAX6 gene deletions involving only one or a few exons. At GeneDx, Multiplex Ligation-dependent Probe Amplification (MLPA) or ExonArrayDx are available for identifying such submicroscopic whole or partial PAX6 gene deletions. While heterozygous PAX6 mutations typically cause aniridia, homozygous PAX6 mutations were also found in a few patients with syndromic anophthalmia.
For further genetic testing in anophthalmia or microphthalmia, GeneDx also offers mutation analysis of the SOX2 (sequence analysis and deletion/duplication testing) and deletion/duplication testing for the SIX6 gene. In addition, sequence analysis and deletion/duplication testing of the PITX2 and FOXC1 genes are available for patients with
anterior segment dysgenesis (Axenfeld-Rierger syndrome, Peters anomaly and Iris hypoplasia)