Phenotypic Characteristics as a Diagnostic Tool for Albinism: Sensitivity and Specificity Analysis

Abstract

Purpose : Albinism has significant genetic and phenotypic heterogeneity and can be difficult to distinguish from other causes of infantile nystagmus, particularly in a paediatric setting. Children with albinism are at risk of poor visual development and hence require timely diagnosis. We sought to identify clinical parameters specific to albinism, in order to contribute to the growing need for international consensus guidelines for the diagnosis of this complex condition.

Methods : Patients with nystagmus presenting to a paediatric ophthalmology department were screened in centres including Denmark, Korea, Netherlands, United Kingdom and the United States. Patients were stratified according to diagnosis through genetic confirmation. Ophthalmic examination, foveal hypoplasia (FH) and visual evoked potentials (VEP) were recorded. Receiver operating characteristic curves were plotted to assess the diagnostic ability of clinical parameters. Principal component analysis was used to identify unique-most variables. A binary logistic regression model was used to identify a single combined metric.

Results : 249 patients were included, of which 63% had molecular confirmation of albinism. Other diagnoses included FRMD7 (17%), PAX6 (8%), achromatopsia (8%) and congenital stationary night blindness (4%). Parameters with a positive correlation with albinism included fundus hypopigmentation (AUC=0.91), transillumination defect (TID) (AUC=0.91), FH (AUC=0.82) and VEP misrouting (AUC=0.73). Parameters with weak correlation included stereopsis (AUC=0.64), visual acuity (AUC=0.53) and altered head position (AUC=0.43). Regression modelling identified a single metric incorporating FH, TID and VEP with the highest predictive power (AUC=0.96). Removing VEP from the model revealed an AUC of 0.95.

Conclusions : Combining FH and TID may provide sufficient diagnostic power in suspected albinism and dismiss other causes of congenital nystagmus. VEP misrouting may only provide a marginal improvement in diagnostic ability.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.