Abstract
Purpose: :
To report the variability of clinical findings, results of wide-field retinal imaging and successful long-term treatment of macular edema in a German family with autosomal dominant vitreoretinochoroidopathy (ADVIRC) harbouring a heterozygous c.256G>A missense mutation in the bestrophin-1 (BEST1) gene.
Methods: :
Three affected members of a four-generation ADVIRC family (mother, son, granddaughter) were examined clinically. Sanger sequencing of the coding and flanking intronic regions of the BEST1 gene was performed.
Results: :
Disease manifestations presented with high variability in mother, son and granddaughter. The mother noted visual problems at age 10, whereas the son had no visual problems up to the age of 40. The granddaughter noted visual problems due to refractive error without ADVIRC related macular alterations. The mother and the granddaughter showed marked signs of peripheral degeneration, while this retinal area was not noticeably affected in the son. In addition, a cystoid macular edema was present in the mother, which responded to long-term local treatment with dorzolamide with improvement of visual acuity. Wide-field fundus autofluorescence and near-infrared autofluorescence revealed mid-peripheral retinal degeneration in areas that appeared normal on ophthalmoscopy. The full-field ERG was markedly reduced in mother and son. Direct sequence analysis of the BEST1 gene revealed a heterozygous c.256G>A missense mutation in the three affected family members.
Conclusions: :
The findings in this family emphasize the previously noted variability of clinical manifestations in BEST1-associated ADVIRC and the relevance of fundus and near-infrared autofluorescence imaging for early detection of areas with retinal degeneration. Cystoid macular edema and vascular leakage can be successfully treated in patients with ADVIRC using dorzolamide.
Keywords: retinal degenerations: hereditary • imaging/image analysis: clinical • genetics