M. Votruba et al., CLINICAL-FEATURES IN AFFECTED INDIVIDUALS FROM 21 PEDIGREES WITH DOMINANT OPTIC ATROPHY, Archives of ophthalmology, 116(3), 1998, pp. 351-358
Objective: To assess phenotypic variation of affected individuals from
British families with autosomal dominant optic atrophy. Design: Eight
y-seven patients from 21 families showing evidence of linkage to chrom
osome 3q were identified via the Genetic Clinic of Moorfields Eye Hosp
ital, London, England. Genetic linkage analysis was carried out with m
arkers from chromosome 3q28-qter. Patients underwent clinical examinat
ion and psychophysical and electrophysiological testing. Results: Best
-corrected visual acuity ranged from 20/20 (6/6 m) to light perception
. Although visual acuity was not significantly worse in older patients
in the group (chi(2) = 3.20, df = 4, P > .50), it did deteriorate wit
h age in one third of the families. Subtle or temporal pallor of the o
ptic disc occurred in 96 (55%) of 174 eyes and total atrophy in 76 (44
%). Tritanopia was found in 6 (7.5%) of 80 patients; 65 (81.2%) had a
mixed color deficit. A cecocentral scotoma was found in the vast major
ity. Peripheral motion detection threshold was elevated in areas of vi
sual field with raised mean surround sensitivity but not elsewhere. Pa
ttern visual evoked potentials were of reduced amplitude and delayed.
Pattern electroretinograms showed a reduced N95 component in keeping w
ith primary ganglion cell dysfunction. Conclusions: There is wide intr
afamilial and interfamilial phenotypic variation in autosomal dominant
optic atrophy, with visual function in some, but not all, families de
teriorating with age. There is evidence of degeneration of the ganglio
n cell layer predominantly from central retina, but this is not the ex
clusive result of either parvocellular or magnocellular cell loss.