Clinical Characteristics
Ocular Features
A 17-year-old male with this condition was diagnosed at the age of two years with bilateral iris hypoplasia. Cataracts were seen at the age of 17 years. There was no foveal depression.
In a 5 generation Chinese family there were additional signs including optic atrophy, ectopia lentis, pigmentary retinopathy, and ‘dysplasia’ of the trabecular meshwork in 5 members.
Systemic Features
No systemic abnormalities have been reported. A single extensively studied patient, who had no developmental problems, was normal by renal ultrasound, audiometric studies, and neurologic evaluations.
Genetics
Inheritance
Autosomal dominant aniridia is the result of PAX6 (a transcription regulator gene) dysfunction. In the majority of cases there are mutations in the PAX6 gene itself as in AN1. There are reports, however, of familial aniridia in which direct PAX6 mutations have been excluded. Two additional forms of aniridia in which there are alterations in genes that modulate the expression of PAX6 have been reported. AN2 described here with mutations in ELP4, a nucleotide variant within an intron of the ELP4 gene (11p13) located distal to the 3-prime end of the PAX6 gene, plus AN3 (617142) with mutations in TRIM44. Both ELP4 and TRIM44 are regulators of the PAX6 transcription gene.
Aniridia 2 has been reported in one patient with a nucleotide variant within an intron of the ELP4 gene (11p13) located distal to the 3-prime end of the PAX6 gene. The gene product is a cis-regulatory enhancer.
Other evidence for aniridia resulting from regulatory modification of PAX6 gene function comes from families in which there are structural alterations such as deletions in chromosome 11, downstream of the PAX6 gene location.
Pedigree
Autosomal dominant
Autosomal dominant disorders require only one mutation for the disease to be expressed. Since an affected parent has two chromosomes, only one of which has the mutant gene, parents can expect that half (50%) of their children will receive that one and inherit the disease. It is common for individuals that inherit the mutation, however, to not have evidence of the disease (nonpenetrance).
Autosomal dominant inheritance leads to a vertical pattern of transmission