Autosomal-dominant iridogoniodysgenesis and Axenfeld-Rieger syndrome are genetically distinct.

PURPOSE

To determine whether there is a locus for iridogoniodysgenesis (IGD)/ familial iris hypoplasia in the region of the known Axenfeld-Rieger syndrome (ARS) locus at 4q25 and to determine the ocular phenotype within the autosomal-dominant iris hypoplasia group of disorders.

METHODS

Clinical examinations were performed on 27 members, with 11 affected from one family in which the IGD occurred in association with the nonocular features of ARS, and on 70 members with 30 affected from a second IGD family with ocular features only. Family members were genotyped for markers within the 4q25 region known to contain a locus for ARS. LOD scores were calculated with the MLINK option of the LINKAGE program.

RESULTS

The iris hypoplasia in each IGD family was similar. In the IGD family with only ocular features (IGD anomaly), however, a majority of those affected had a goniodysgenesis with excess tissue in the angle and anomalous angle vascularity. These findings were absent in the IGD family with syndromic features (IGD syndrome). Linkage to the 4q25 region was excluded in the IGD anomaly family, whereas the family with IGD syndrome was found to be completely linked to the 4q25 region (peak LOD score with D4S407 of 7.827 at theta = 0.00).

CONCLUSIONS

The authors' results suggest that mutations at the 4q25 locus can result in variable ocular features that also occur in combination with nonocular (dental and jaw) anomalies. Mutation of a separate locus must underlie IGD with ocular features only. A re-evaluation of the relation between the various forms of autosomal-dominant iris hypoplasia, therefore, may be warranted.