Retinal ciliopathy due to mutation in the RPGRIP gene

Retinal ciliopathy due to mutation in the RPGRIP1 gene (also known as RPGRIP1-related retinal dystrophy or Leber congenital amaurosis type 6, LCA6) is a rare inherited eye disorder caused by mutations in the RPGRIP1 (retinitis pigmentosa GTPase regulator-interacting protein 1) gene. RPGRIP1 encodes a protein that is essential for the normal structure and function of the connecting cilium in photoreceptor cells of the retina. When this protein is absent or dysfunctional, photoreceptors degenerate, leading to severe visual impairment. The condition primarily affects the visual system. Patients typically present in infancy or early childhood with severely reduced vision or near-blindness, nystagmus (involuntary rhythmic eye movements), sluggish or absent pupillary light responses, and a markedly abnormal or extinguished electroretinogram (ERG). The retinal appearance may initially seem relatively normal but progressively shows signs of retinal degeneration, including pigmentary changes, attenuated retinal vessels, and optic disc pallor. Some patients may also exhibit photophobia, hyperopia, and the oculodigital sign (eye pressing or rubbing), which is commonly seen in children with Leber congenital amaurosis. Currently, there is no approved cure for RPGRIP1-related retinal ciliopathy, and management is primarily supportive, including low-vision aids, educational accommodations, and orientation and mobility training. However, RPGRIP1 is being actively investigated as a target for gene therapy, with preclinical studies and early-phase clinical trials exploring the potential of delivering a functional copy of the gene to retinal cells. Genetic counseling is recommended for affected families to discuss recurrence risks and emerging therapeutic options.

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