Is pseudoexfoliation syndrome inherited? A review of genetic and nongenetic factors and a new observation

Abstract

Pseudoexfoliation (PEX) syndrome is the commonest identifiable cause of open-angle glaucoma worldwide. PEX is characterized clinically by small whitish deposits of fibrillar-granular material in the anterior segment of the eye. Despite its prevalence and potential for ophthalmic morbidity, surprisingly little is known about the etiology and pathogenesis of PEX. This article reviews the literature and presents evidence regarding genetic and nongenetic arguments for the etiology of pseudoexfoliation. Lines of evidence that support a genetic basis for PEX include transmission in two-generation families, twin studies, an increased risk of PEX in relatives of affected patients, and HLA studies. Nearly all pedigrees in the literature, and our own experience with PEX families in Iceland and Canada, suggest maternal transmission, raising the possibilities of mitochondrial inheritance, X-linked inheritance, and autosomal inheritance with genomic imprinting. A number of nongenetic factors have also been evaluated for their possible implication in the development of PEX. These include ultraviolet light, autoimmunity, slow virus infection, and trauma. It is possible that a combination of genetic and nongenetic factors may be involved in the etiology and pathogenesis of PEX, i.e. it may be a multifactorial disorder. Further studies with larger numbers of patients are needed to delineate more clearly the contribution of genetic (nuclear DNA, mitochondrial DNA or both) and nongenetic factors to the development of pseudoexfoliation syndrome and pseudoexfoliation glaucoma.

Serum YKL-40 levels as a novel marker of inflammation and endothelial dysfunction in patients with pseudoexfoliation syndrome

“…28,29 Cumurcu et al 30 displayed that serum a 1-antitrypsin, an acute phase protein associated with inflammatory processes, was significantly higher in PEX patients than in controls. Fiore et al 31 found that eyes with PEX had a greater post-laser inflammatory reaction than eyes without PEX.…”

Epidemiology of the pseudo-exfoliation syndrome, A review

“…Along with the observation of two homozygote pairs of twins, one concordant and one discordant for the presence of PE syndrome, this was taken to indicate an environmental influence on the distribution of the PE syndrome (Ringvold et al 1988). However, as indicated recently by Damji et al (1998), it is possible that a combination of genetic and nongenetic factors may be involved in the etiology and pathogenesis of the PE syndrome, i.e. it may be a multifactorial disorder.…”

Genome-wide association study with DNA pooling identifies variants at CNTNAP2 associated with pseudoexfoliation syndrome

“…2 The etiology of PEX syndrome is still poorly understood but increased prevalence of the disease in certain populations and observed familial aggregation are compatible with PEX being a complex genetic disorder. [3][4] Proteomic approaches identified the presence of elastic fiber components (such as fibrillin-1, vitronectin and fibulin-2), clusterin as well as apolipoprotein E (APOE) within PEX material deposits, suggesting them as possible functional candidate genes for PEX disease. [5][6] To date however, among these candidates only polymorphisms in the gene encoding for clusterin (CLU) have been shown to be associated both with PEX syndrome and PEX glaucoma (PEXG) in different populations.…”