Phenotype-phenotype and genotype-phenotype correlations in patients with idiopathic superior oblique muscle palsy

Idiopathic superior oblique muscle palsy presents, as quantitative phenotypes, vertical deviation and cyclodeviation in eye alignment on clinical testing, and superior oblique muscle hypoplasia on imaging. We determined ARIX and PHOX2B polymorphisms as genotypes, and analyzed phenotype-phenotype and genotype-phenotype correlations in 37 patients with idiopathic superior oblique muscle palsy. Vertical deviations were measured at upright position of the head and head tilt for 30° to either side, and angles of objective excyclodeviations were determined by image analysis on fundus photographs. Cross-sectional areas of the superior oblique muscle near the eye globe-optic nerve junction were measured by image analysis on coronal sections of magnetic resonance imaging to calculate the paretic-side/normal-side ratios. Among the phenotypes, the increase in vertical deviations elicited by head tilt to the paretic side, the decrease in vertical deviations elicited by head tilt to the normal side and the difference of angles of objective excyclodeviations between the paretic side and normal side were significantly correlated inversely with the paretic-side/normal-side ratios of the cross-sectional areas of the muscle (r=-0.43 with P=0.0084, r=-0.34 with P=0.038, and r=-0.43 with P=0.009, respectively, n=37, Pearson's correlation test). Fifteen patients with ARIX and/or PHOX2B polymorphisms had significantly greater paretic-side/normal-side ratios of the muscle compared with 20 patients without the polymorphisms (P=0.017, n=35, Mann-Whitney U-test). The patients with ARIX and/or PHOX2B polymorphisms had less hypoplastic superior oblique muscles.