Inherited, familial and sporadic primary open-angle glaucoma

The U.S. surgeon general has recently launched a campaign to promote the awareness of the medical value of family history. Further attention should be paid to familial aggregation. Accordingly, we suggest that primary open-angle glaucoma (POAG) be classified into inherited, familial and sporadic categories. The three classes of POAG differ not only in inheritance pattern and familial aggregation but also in methodology and outcome of gene mapping. Inherited POAG follows Mendelian inheritance and has been linked to seven chromosomal loci to date by linkage analysis. Familial POAG does not show a clear pattern of Mendelian inheritance and is typically studied by sib-pair analysis and family-based association analysis, although the results often require replication in multiple samples. Interestingly, many sporadic POAG cases carry known POAG-causing mutations, suggesting genetic predisposition as well. Based on published data, we estimated that inherited and familial POAG cases may account for approximately 72% of all POAG cases. We further formulated a mathematic model to estimate disease prevalence and mutation frequency taking both ethnic background and familial aggregation into consideration. Conclusion: POAG appears to be mainly caused by genetic predisposition in interaction with other risk factors such as age. The suggested classification of POAG may serve as a useful guide in clinical practice and genetic studies where ethnic background and familial aggregation must be taken into consideration.