Progressive Retinal and Neurologic Findings in a Family With Neuropathy, Ataxia, and Retinitis Pigmentosa Syndrome

To describe the longitudinal ophthalmic findings of a maternally related triad with neuropathy, ataxia, and retinitis pigmentosa and explore potential relationships between phenotype and heteroplasmy levels.

A mother, daughter, and son with genetically confirmed neuropathy, ataxia, and retinitis pigmentosa due to the m.8993T>G MT-ATP6 variant (heteroplasmy levels: 38.8%, 76.8%, and 87%, respectively) were followed for 5 years. Assessments included best-corrected visual acuity, slitlamp examination, dilated fundus examination, optical coherence tomography, widefield color fundus imaging, fundus autofluorescence, full-field and multifocal electroretinography, and Goldmann visual field testing.

Longitudinal evaluation demonstrated marked intrafamilial variability. Patient 1 demonstrated widespread ellipsoid zone loss and rod-cone dysfunction; Patient 2 exhibited retinal thinning and cone-predominant dysfunction. Patient 3 showed initially normal retinal structure with subtle fundus autofluorescence changes and mild asymmetric functional loss.

Despite harboring the same pathogenic MT-ATP6 variant, affected family members exhibited substantial variability in ophthalmic disease severity. Clinical manifestations did not correlate with blood heteroplasmy levels, highlighting the importance of longitudinal multimodal ophthalmic surveillance in patients with neuropathy, ataxia, and retinitis pigmentosa.