Familial Transmission Patterns of Infantile Glaucoma in Australia

Abstract

Abstract: : Purpose: The CYP1B1 gene has been implicated in primary infantile (or congenital) glaucoma (IG), whilst mutations in other genes such as PITX2, FKHL7, and PAX6 cause iridotrabeculodysgenesis (ITD) and secondary IG. Identification of gene mutations allows prenatal advice regarding recurrence risk and mode of inheritance. However, in the clinical setting where the causative gene mutation is usually unknown, the clinician is often confronted by the question: "If I have IG, are my children at risk?" The purpose of this study was to determine the likelihood of a person in Australia who has IG producing a child who also manifests the disease. Methods: A retrospective cross–sectional design was utilized. The pedigrees of probands from Southeastern Australia, who were diagnosed with IG since 1980, were reviewed. Pedigrees were categorised according to the presence or absence of ITD. Exclusion criteria included incomplete pedigree phenotype information, or aphakic glaucoma following congenital cataract surgery. Fisher’s exact test was used to compare the parent–offspring phenotype transmission between ITD IG and primary IG. Results: Seventy–three probands were identified, however 3 pedigrees were excluded due to incomplete phenotype information. There were statistically significantly (P<0.05) more ITD IG pedigrees with direct parent–offspring transmission of phenotype (6 from 11). Five percent (3 from 59) of pedigrees with primary IG were found to have parent–offspring phenotype transmission. Conclusions: This clinical audit has revealed that Australian patients with ITD IG are at a greater risk of having children with IG than those patients with primary IG. Primary IG is thought to be autosomal recessive, thus it was surprising for an outbred population to have a "dominant" transmission in 5% of cases. The precise probability for offspring having the same IG phenotype as their parent could be inferred through investigating the mutated allele frequency in the population.

Keywords: genetics • clinical (human) or epidemiologic studies: prevalence/incidence