Female heterozygotes of X‐linked ocular disease in the era of molecular diagnostics

Purpose To investigate the accuracy of recognizing female heterozygotes for X‐linked retinitis pigmentosa (XLRP) and choroideraemia (CHM) using fundoscopy and blue‐light fundus autofluorescence (FAF). Methods Retrospective analysis revealed 26 female XLRP heterozygotes from 17 different families (age 3–77 years) and 8 CHM heterozygotes from 5 families (age 14–65 years). Molecular diagnosis has been obtained for all subjects. Results In XLRP, 17 of 26 patients (65.4%) mentioned nyctalopia. RPGR mutations were identified in 18 subjects – 9 of which in ORF15 – whereas a causative mutation was found in RP2 in the remaining 8 subjects. Dilated fundoscopy showed no abnormalities in 8 subjects, a tapetoid reflex in 2, regional pigmentary changes in 16 and full‐blown RP features in 2 patients. An abnormal FAF pattern was found in 18 of 26 patients (69.2%). Of the 26 molecularly proven heterozygotes, 23 (88.5%) showed abnormalities on fundoscopy and/or FAF. In CHM, only 1 of 8 patients – aged 40 – mentioned visual difficulties at night. In each of the 8 subjects, equatorial mottled pigmentary changes were evident. FAF revealed multiple hyper‐ and hypoautofluorescent flecks in all 8 patients. In both XLRP and CHM, clinical findings were independent of age or specific mutation. Conclusions Female heterozygotes of XLRP show abnormalities on dilated fundoscopy and/or blue‐light fundus autofluorescence in 88.5% of cases with a molecularly proven diagnosis. The most characteristic feature is a radial pattern of alternating areas of hyper‐ and hypoautofluorescence. In CHM, all carriers exhibit pigmentary changes in the retinal midperiphery and scattered autofluorescence changes, despite a lack of visual symptoms.