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, and to define diagnostic criteria for the Caucasian population. We also estimated the prevalence of albinism in the Netherlands.

DESIGN: Retrospective cohort study.

SUBJECTS: We investigated the phenotype of 522 albinism patients 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 electrophysiological data of albinism patients. We used grading schemes for iris translucency, fundus hypopigmentation, and foveal hypoplasia.

MAIN OUTCOME MEASURES: Visual acuity (VA), nystagmus, iris translucency, fundus pigmentation, foveal hypoplasia and misrouting.

RESULTS: In 7.7% (40/521) nystagmus was absent, 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 in 16.1% (49/304) misrouting was not established. The VA varied from -0.1 to 1.3 logMAR. The foveal hypoplasia grading correlated best with the VA (r=0.69, p < 0.001), while 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 three major criteria, or two major and two minor criteria are necessary for the diagnosis. In the presence of a molecular diagnosis, one major criterion or two minor criteria will be sufficient.