Five-Year Structural Progression in Monozygotic Twins with MAK Exon 3- Related Retinitis Pigmentosa

Background Retinitis Pigmentosa (RP) associated with variants in the MAK gene is a relatively uncommon form of inherited retinal degeneration, although certain variants are more prevalent in specific populations. The only reported cases are linked to a homozygous Alu insertion in exon 9, whereas the clinical course and structural progression associated with exon 3 variants have not been described. Longitudinal imaging studies in genetically identical individuals are particularly rare. We report a five-year structural retinal progression in monozygotic twins with RP associated with a genetically confirmed exon 3 deletion in the MAK gene. Case presentation Two monozygotic twin brothers aged 47 years presented with progressive nyctalopia and peripheral visual field constriction beginning at approximately 38 years of age. Neither patient had systemic disease or extraocular manifestations. At the most recent evaluation, best-corrected visual acuity was 0.3 (6/12) in both eyes of both patients. Anterior segment examination and intraocular pressure were normal. Fundus examination revealed classic signs of RP, including optic disc pallor, attenuation of retinal vessels, and peripheral bone-spicule pigmentation. Genetic testing identified a homozygous exon 3 deletion in the MAK gene, confirmed by segregation analysis. Multimodal retinal imaging, including fundus autofluorescence (FAF) and spectral-domain optical coherence tomography (SD-OCT), demonstrated progressive contraction of the ellipsoid zone (EZ) and thinning of the outer retinal layers over a five-year follow-up period. Structural progression was highly concordant between the twins, while central visual acuity remained relatively preserved with relatively mild deterioration of the visual field. Conclusions This report documents longitudinal structural retinal degeneration in monozygotic twins with RP associated with exon 3 deletion in the MAK gene. Imaging biomarkers, particularly EZ integrity on OCT, may detect disease progression earlier than visual acuity changes. These findings contribute to understanding the natural history of this rare genetic variant and highlight the value of multimodal imaging in monitoring inherited retinal diseases.