Case Report

IMPG1-c.847dup and Vitelliform Macular Dystrophy type 4: Multimodal Characterization and a Review of the Literature

Authors: Piero Barrera-Arshavin, Eduardo Urrejola-Irarrazabal, María J Rivas-Figueroa, Juan I Verdaguer-Díaz.

DOI: 10.33425/2768-6647.1068

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Abstract

Adult-onset vitelliform macular dystrophy (AOVMD) encompasses several genetic entities. The autosomal-dominant subtype 4 is produced by heterozygous truncating variants in the IMPG1 gene, leading to sialoprotein associated with the photoreceptor layer (SPACR) loss-of-function and haploinsufficiency.

Case Report: A 49-year-old woman presented with yellow photopsias and progressive visual loss, more pronounced in the left eye (OS). Spectral-domain optical coherence tomography disclosed ellipsoid-zone disruption with a sub-foveal deposit; fundus autofluorescence showed a hypo-fluorescent ring without the peripheral flecks typical of Stargardt disease. Fullfield electroretinography revealed generalized rod-cone dysfunction without pathologic b-wave inversion. Targeted nextgeneration sequencing (330-gene panel) identified the pathogenic duplication IMPG1-c.847dup; no pathogenic variants were found in ABCA4, antiretinal antibodies were negative and systemic malignancy was excluded. During 14 months of follow-up, central foveal thickness declined by 24 µm (3 µm/month) and visual acuity remained stable with low-vision rehabilitation.

Discussion: Clinical and imaging features match vitelliform macular dystrophy type 4 and differ clearly from autoimmune retinopathy, ABCA4-related Stargardt disease, PRPH2-linked maculopathy and hydroxychloroquine toxicity. Molecular confirmation obviated empirical immunosuppression, enabled accurate family counseling (50 % transmission risk) and may qualify the patient for forthcoming adeno-associated viral gene-therapy trials targeting IMPG1 projected to start in 2026.

Conclusion: A single heterozygous frameshift duplication, IMPG1-c.847dup, is sufficient to cause AOVMD subtype 4. Integrating multimodal retinal imaging with next-generation sequencing provides a definitive diagnosis and supports personalized management.

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