To describe the phenotype of Best vitelliform macular dystrophy (BVMD) and to evaluate genotype–phenotype and histopathologic correlations.
Retrospective analysis of patients with BVMD who underwent an extensive ophthalmic examination, including best-corrected Snellen visual acuity, fundus examination by indirect ophthalmoscopy, fundus photography, fundus autofluorescence, optical coherence tomography, fundus fluorescein angiography, and electrooculography. In addition, molecular genetic analysis of the BEST1 gene was performed in all patients.
We examined 40 eyes of 20 patients with BVMD. Sixteen eyes (40%) had a well-defined BVMD stage, whereas 18 eyes displayed characteristics attributable to different stages. Six eyes had an atypical form of BVMD. Fundus autofluorescence and optical coherence tomography frequently detected abnormalities that were not visible on ophthalmoscopy. All patients carried a mutation in the BEST1 gene. Molecular genetic analysis identified 8 different BEST1 mutations in 15 families, including 2 novel mutations (p.Gly299Ala and p.Ile3Thr). Genotype–phenotype correlation was limited, as we observed a broad phenotypic range in association with a single BEST1 mutation. However, the p.Ala243Val seems to cause a mild and relatively invariable BVMD phenotype.
A broad phenotypic variability may be observed in BVMD, even with a single BEST1 mutation. Fundus autofluorescence and optical coherence tomography are valuable noninvasive imaging techniques for phenotyping and follow-up of BVMD patients.
In this study, most best vitelliform macular dystrophy patients simultaneously displayed characteristics of different Best vitelliform macular dystrophy stages. Fundus autofluorescence and optical coherence tomography were able to visualize abnormalities in Best vitelliform macular dystrophy that were not detected on ophthalmoscopy. A broad phenotypic variability may be observed in association with a single mutation in the BEST1 gene.
From the *Department of Ophthalmology; †Department of Human Genetics, Radboud University Nijmegen Medical Centre, Nijmegen; ‡Department of Ophthalmology, Academic Medical Center, Amsterdam; and §Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
This study was financially supported by the Gelderse Blindenvereniging, the Landelijke Stichting voor Blinden en Slechtzienden, the Rotterdamse Vereniging Blindenbelangen, the Stichting Blindenhulp, and the Stichting Ondersteuning Oogheelkunde’s Gravenhage. The funding organizations had no role in the design or conduct of this research.
None of the authors have any financial, commercial, or proprietary interests to disclose.
Reprint requests: Camiel J. F. Boon, MD, Department of Ophthalmology, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands; e-mail: C.Boon@ohk.umcn.nl