Background: Genetic factors may play an important role in pseudoexfoliation syndrome. We describe the familial occurrence of pseudoexfoliation in Canadian families.
Methods: Probands with pseudoexfoliation were referred to a tertiary care glaucoma service in Ottawa because of a family history of pseudoexfoliation or glaucoma, or both. Probands and family members who agreed to participate underwent a systematic interview and eye examination. The pseudoexfoliation status was classified as affected, suspect or unknown based on preestablished criteria for the diagnosis of pseudoexfoliation and glaucoma.
Results: Thirty-four members of 10 families were assessed (18 affected, 2 suspect and 14 status unknown). Six families had two or more generations with pseudoexfoliation, and four families had one generation affected. There was a predominance of females among the affected subjects (17:1), and transmission in all cases appeared to be maternal. Eight of the families were of Irish/Scottish ancestry. Nine (50%) of the affected subjects had cardiovascular disease. Affected subjects tended to be older than suspects and those whose status was unknown (mean age 77, 67 and 55 years respectively). Seven subjects were affected unilaterally and 11 bilaterally. Affected subjects had moderate angle pigmentation in both eyes (mean +2.7, where 0 = no pigment and +4 = dense homogeneous pigment). The mean intraocular pressure in both eyes was higher for the affected subjects (23.1 [standard deviation (SD) 8.6] mm Hg) than for the suspects (16.8 [SD 6.1] mm Hg) and those of unknown status (16.8 [SD 2.9] mm Hg). An enlarged cup:disc ratio was seen in the affected subjects (mean 0.62). Eleven (61%) of the affected subjects had open angles on gonioscopy, and five had occludable angles and required peripheral iridectomy. Ten (56%) of the affected subjects were classified as having glaucoma, and 14 (78%) had evidence of cataract formation in at least one eye.
Interpretation: Pseudoexfoliation appears to be transmitted matrilineally, which raises the possibility of mitochondrial inheritance, X-linked inheritance or autosomal inheritance with genomic imprinting. A larger study of families with pseudoexfoliation is necessary to clarify the mode of transmission and to identify the gene(s) involved in the etiology of this disorder.