BEST1-related autosomal dominant vitreoretinochoroidopathy: a degenerative disease with a range of developmental ocular anomalies.

PURPOSE: To describe the spectrum of phenotypic characteristics of BEST1-related autosomal dominant vitreoretinochoroidopathy (ADVIRC) in a family with p.V86M mutation.
METHODS: A retrospective review of the clinical, psychophysical, and electrophysiological phenotypes of six subjects with ADVIRC. Five family members were sequenced for mutations in the BEST1 gene.
RESULTS: A heterozygous change, p.V86M (c.256G > A), was identified in the BEST1 gene in the three affected subjects tested, and was shown to segregate with the disease phenotype. The distance visual acuity ranged from ≥ 20/25 to absent perception of light. Clinical features observed included angle closure glaucoma (n = 2), microcornea with shallow anterior chamber (n = 1), iris dysgenesis (n = 2), cataracts (n = 4), classical peripheral concentric band of retinal hyperpigmentation (n = 5), and optic nerve dysplasia (n = 1). Full-field electroretinogram response amplitudes ranged from low normal (two cases; 27 and 32 years) to non-recordable (two cases; 42 and 63 years). Goldmann fields were normal in two (27 and 28 years) but were abnormal in two older subjects. Optical coherence tomography showed macular thinning in the proband, whereas his affected daughter had normal macular thickness. Electro-oculography showed borderline Arden's ratio (1.50) in the lone case tested (27 years).
CONCLUSION: ADVIRC is a slowly progressive vitreoretinal degeneration that demonstrates marked intra-familial phenotypic variability. Optic nerve dysplasia and iris dysgenesis are novel observations that extend the ocular phenotype of ADVIRC.