Intrafamilial Variability of IMPG1-Associated Vitelliform Dystrophy

Abstract

Purpose: To describe the clinical and multimodal imaging findings of two siblings with different vitelliform phenotypes associated with a novel IMPG1 gene deletion.

Methods: Case series of two siblings. Patients underwent standard optical coherence tomography (OCT), fundus color and short-wavelength fundus autofluorescence (SW-FAF) imaging, fluorescein angiography, and genetic testing for a panel of inherited retinal disorders.

Results: A 43-year-old brother and his 41-year-old sister were found to have bilateral vitelliform lesions. The brother presented with single bilateral foveal lesions whereas his asymptomatic sister had multifocal extrafoveal lesions. OCT imaging demonstrated classic subretinal vitelliform lesions in various stages. SW-FAF confirmed that the lesions were hyperautofluorescent. Genetic testing identified an identical heterozygous exon 7 deletion of IMPG1 in both patients.

Conclusion: Segregation of a novel deletion in exon 7 of IMPG1 in a family with a vitelliform macular dystrophy, together with a previously reported similar phenotype in patients with heterozygous nucleotide changes within this region of the gene supports the pathogenicity of this variant. Intrafamilial variability in the topography of the lesions with multifocality in one of the siblings suggests retina-wide abnormalities with individual modifiers modulating disease expression.

Keywords: AFVD; Adult onset foveomacular vitelliform dystrophy; IMPG1; Interphotoreceptor matrix proteoglycan 1; Macular dystrophy; VMD; Vitelliform.