Intrafamilial variation of phenotype in Stargardt macular dystrophy-Fundusflavimaculatus

PURPOSE. TO evaluate the intrafamilial phenotypic variation in Stargardt ma cular dystrophy-Fundus flavimaculatus (SMD-FFM). METHODS. Thirty-one siblings from 15 families with SMD-FFM were examined. A ge of onset, visual acuity, and clinical features on fundus examination and fundus autofluorescence images, including presence or absence of central a nd peripheral atrophy and distribution of flecks, were recorded. In additio n, electrophysiological studies were undertaken. RESULTS. Large differences between siblings in age of onset (median, 12 yea rs; range, 5-23 years) were observed in six of the 15 families studied, whe reas in 9 families differences in age of onset between siblings were small (median, 1 year; range, 0-3 years). Visual acuity varied two or more lines among siblings in nine families. In 10 families (67%) siblings were found t o have different clinical appearance on fundus examination and fundus autof luorescence images, whereas in 5 families (33%), affected siblings had simi lar clinical features. Electrodiagnostic tests were performed on affected m embers of 12 families and disclosed similar qualitative findings among sibl ings. In nine families there was loss of central function only; in two, glo bal loss of cone function; and in one, global loss of cone and rod function . CONCLUSIONS. In this series, although differences in age of onset, visual a cuity, and fundus appearance were observed between siblings, electrophysiol ogical studies demonstrated intrafamilial homogeneity in retinal function. The findings are difficult to reconcile with expression studies showing ABC R transcripts in rod photoreceptors but not in cones.