Phenotypic Presentation of Autosomal Dominant Optic Atrophy in Two Large Canadian Pedigrees.

Abstract

Abstract: : Purpose: To evaluate the phenotypic variability in two large Canadian Maritime pedigrees with autosomal dominant optic atrophy (ADOA) and to test the hypothesis that a phenotype/genotype association exists for ADOA. Methods:The first pedigree (I), comprised of twenty–three affected and seventeen non–affected members, could not be linked to either the OPA1 or OPA4 loci, while pedigree (II) could be linked to the OPA1 locus with 12 of 12 affected individuals testing positive for a mutation in OPA1 (2826delT). None of the 36 unaffected members of pedigree (II) demonstrated any genetic change. Genetic screening and clinical ocular assessments were performed on all individuals (N=88). Psychophysical tests such as color vision (n=73), contrast sensitivity (n=27), Goldman perimetry (n=25) were performed, as well as electrophysiological assessments including Ganzfeld–electroretinograms (n=21), multifocal electroretinograms (n=11) and visual evoked potentials (n= 29). Results:Of the 35 affected individuals (pedigrees I and II), only 29%(I) 41%(II) had a visual acuity worse than 6/9, while 32%(I) 60%(II) showed moderate to severe color vision loss, 33%(I) 100%(II) contrast sensitivity loss, 25%(I) 75%(II)% changes in optic nerve appearance and 53%(I) 37%(II) Goldman perimetry anomalies. On electrophysiological testings, 46%(I) 54%(II) showed visual evoked potentials delays, 82%(I) 30%(II) reduced rod–isolated electroretinographic responses and 75%(I) 57%(II) mild changes in multifocal topography maps. Of the unaffected individuals from the two pedigrees, 10% showed mild color defects while 13% were found as having mild optic nerve head anomalies. Conclusions:Patients in these two ADOA pedigrees showed a wide spectrum of phenotypic presentation. However, family members carrying the known OPA1 mutation appeared to suffer more severe visual perception disabilities, while affected members of the family who failed to map to either OPA1 or OPA4 appeared to have more retinal involvement. This suggests the presence of a phenotype–genotype association in ADOA.

Keywords: genetics • neuro–ophthalmology: diagnosis • degenerations/dystrophies