AUTOSOMAL-DOMINANT IRIDOGONIODYSGENESIS AND AXENFELD-RIEGER SYNDROME ARE GENETICALLY DISTINCT

Purpose: To determine whether there is a locus for iridogoniodysgenesi s (IGD)/familial iris hypoplasia in the region of the known Axenfeld-R ieger syndrome (ARS) locus at 4q25 and to determine the ocular phenoty pe within the autosomal-dominant iris hypoplasia group of disorders. M ethods: Clinical examinations were performed on 27 members, with 11 af fected from one family in which the IGD occurred in association with t he nonocular features of ARS, and on 70 members with 30 affected from a second IGD family with ocular features only, Family members were gen otyped 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 fa mily with IGD syndrome was found to be completely linked to the 4q25 r egion (peak LOD score with D4S407 of 7.827 at theta = 0.00). Conclusio ns: 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 mu st underlie IGD with ocular features only, A re-evaluation of the rela tion between the various forms of autosomal-dominant iris hypoplasia, therefore, may be warranted.