A full-thickness macular hole is conventionally regarded as a vitreoretinal-interface disorder of later life caused by anomalous perifoveal posterior vitreous detachment, tangential traction, and failure of foveal tissue compliance. This model explains idiopathic macular holes. Secondary macular holes could occur secondary to trauma, retinal detachment and high myopia, but less is known about the nature of macular holes associated with inherited retinal dystrophies and vitreoretinopathies, in which the fovea, retinal pigment epithelium, basement membranes, or vitreous cortex may be genetically abnormal before traction is applied. We examine evidence on macular holes in inherited retinal disease, with emphasis on genotype, molecular pathology, optical coherence tomography phenotype and surgical strategy. Three mechanistic groups are clinically useful: (i) disorders of basement membrane and vitreoretinal-interface; (ii) disorders characterized by intrinsic neurosensory retinal weakness; and (iii) retinal pigment epithelium-driven outer-retinal disruption. Surgical closure is often possible, particularly when a tractional component is present and outer-retinal structure is preserved. Visual recovery, however, is limited by photoreceptor integrity, retinal pigment epithelium survival, chronicity and the extent of pre-existing degeneration. In select disorders, especially Alport syndrome, standard internal limiting membrane peeling may be impossible or inappropriate, and alternative scaffold techniques such as amniotic membrane graft may be beneficial. Genetic diagnosis helps to inform mechanism, prognosis, operative planning, counselling and eligibility for emerging gene-directed therapies. This framework may help clinicians interpret optical coherence tomography findings and consider disease-specific surgical risks;. however, the evidence base is dominated by case reports and small case series and varies substantially across diagnoses. Accordingly, the proposed classification and management considerations should be viewed as hypothesis-generating and clinically-pragmatic rather than guideline-level recommendations.