The Phenotypic Spectrum of Albinism

Purpose: To describe the phenotypic spectrum of a large cohort of albino patients, to investigate the relationship between the ocular abnormalities and the visual acuity (VA), and to define diagnostic criteria for the white population. We also estimated the prevalence of albinism in The Netherlands. Design: Retrospective cohort study. Participants: We investigated the phenotype of 522 patients with albinism from the databases of Bartiméus (452 patients), Leiden University Medical Center (44 patients), and the Academic Medical Center Amsterdam (26 patients). Methods: We collected clinical, genetic, and electrophysiologic data of patients with albinism. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia. Main Outcome Measures: Visual acuity, nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia, and misrouting. Results: Nystagmus was absent in 7.7% (40/521), iris translucency could not be detected in 8.9% (44/492), 3.8% (19/496) had completely normal fundus pigmentation, 0.7% (3/455) had no foveal hypoplasia, and misrouting was not established in 16.1% (49/304). The VA varied from −0.1 to 1.3 logarithm of the minimum of angle of resolution (logMAR). The foveal hypoplasia grading correlated best with the VA (r = 0.69, P < 0.001), whereas iris translucency, fundus pigmentation, and misrouting did not predict the VA significantly. We estimated a prevalence of albinism in The Netherlands of at least 1:12 000. Conclusions: None of the characteristics of albinism were consistently present in our cohort. To be able to distinguish albinism from other conditions with similar ocular features, especially in northern and western European countries, we propose major and minor clinical criteria. Major criteria would be (1) foveal hypoplasia grade 2 or more, (2) misrouting, and (3) ocular hypopigmentation, either iris translucency or fundus hypopigmentation grade 2 or more. Minor criteria would be (1) nystagmus, (2) hypopigmentation of skin and hair, (3) grade 1 fundus hypopigmentation, and (4) foveal hypoplasia grade 1. We propose that 3 major criteria or 2 major and 2 minor criteria are necessary for the diagnosis. In the presence of a molecular diagnosis, 1 major criterion or 2 minor criteria will be sufficient