Autosomal dominant Stargardt-like macular dystrophy: I. Clinical characterization, longitudinal follow-up, and evidence for a common ancestry in families linked to chromosome 6q14.

PURPOSE: Characterize the phenotype of autosomal dominant Stargardt-like macular dystrophy in two families linked to chromosome 6q14 and determine whether they share a common ancestry.

METHODS

Two families spanning 10 generations were identified and studied independently. Participating members were examined and genetic linkage and genotyping performed.

RESULTS

Presenting symptoms included decreased vision, hemeralopia, and mild photophobia. The subjective onset of visual loss ranged from age 3 to 50 with a mean of 14 years. A Snellen acuity of 20/200 occurred at a mean age of 22 years. Over decades, the macular lesion enlarged and visual acuity decreased to 20/300 to 20/800. The typical phenotype was well-circumscribed, homogenous atrophy of the retinal pigment epithelium and choriocapillaris in the macula, with surrounding yellow flecks and temporal optic nerve pallor. The phenotypic spectrum included a pattern dystrophy-like appearance, diffuse geographic atrophy, and extensive fundus flecks. Genotyping revealed that the two families were linked to chromosome 6q14 and shared a common haplotype spanning 21 cM between D6S430 and D6S300. The two families were subsequently shown by genealogic investigation to represent different branches of a common kindred.

CONCLUSIONS

Families with autosomal dominant Stargardt-like macular dystrophy linked to chromosome 6q14 share a common phenotype and in some cases can be distinguished from similar dystrophies by inheritance pattern and clinical features. The finding that these two families shared a common ancestor suggests the existence of a founder effect. Characterization of the gene for autosomal dominant Stargardt-like macular dystrophy may enable better understanding of this condition and elucidation of its potential role in other forms of macular degeneration.