Retinitis pigmentosa (RP)

Retinitis pigmentosa presents as a progressive rod-cone degeneration with early loss of rod function. The initial symptom is usually impaired dark adaptation (nyctalopia). Mid-peripheral visual-field loss develops next and is often unnoticed until constriction produces tunnel vision. Characteristic fundus changes include arteriolar narrowing, retinal pigment epithelial atrophy, waxy optic-disc pallor and intraretinal bone-spicule pigmentation; the fundus can still appear normal in early disease. Central visual acuity is usually preserved until the late stages, although cystoid macular oedema can reduce it at any age. Retinitis pigmentosa is classified as non-syndromic, syndromic, or systemic. Nonsyndromic forms are confined to the eye, syndromic forms involve additional neurosensory systems such as hearing, and systemic forms affect multiple tissues. Age of onset is highly variable and depends on the genetic subtype and inheritance mode; earlier onset generally predicts a more severe course. It is the most common inherited retinal dystrophy and a major cause of severe visual impairment in people younger than 60 years.

The estimated prevalence of retinitis pigmentosa is 1/3,500 to 1/4,000 in the US and Europe. Non-syndromic forms account for 70-80% of all affected individuals, and the syndromic and systemic forms together account for the remaining 20-30%.

The diagnostic panel comprises more than 100 genes associated with retinitis pigmentosa, reflecting the marked genetic heterogeneity of this disease group. Retinitis pigmentosa may occur as a nonsyndromic disorder with autosomal dominant, autosomal recessive or X-linked inheritance, or as part of a syndromic condition. Frequently implicated genes include RHO in autosomal dominant disease, USH2A in autosomal recessive disease and RPGR in X-linked disease. USH2A is associated with both nonsyndromic retinitis pigmentosa and type II, characterised by retinal degeneration in combination with sensorineural hearing loss. Further relevant genes include EYS and CRB1.

The genetic conditions associated with retinitis pigmentosa follow heterogeneous inheritance patterns, including autosomal dominant, autosomal recessive, and X-linked inheritance. Digenic inheritance is very rare. Many cases are simplex, with no other affected family members and therefore no inheritance pattern evident from the family history. Simplex presentations may result from autosomal recessive or X-linked inheritance, reduced penetrance, or de novo pathogenic variants. In males with simplex retinitis pigmentosa, an underlying X-linked condition, particularly due to a pathogenic variant in RPGR, should be considered.

• Molecular genetic testing can establish the underlying genetic diagnosis, confirm the clinical suspicion, enable predictive testing of at-risk family members and provide information relevant to family planning.
• The identified entity supports condition-specific monitoring and management decisions; therapeutic options are evaluated individually by the treating physicians.

• Fahim AT, Daiger SP, Weleber RG. Nonsyndromic Retinitis Pigmentosa Overview. 2000 Aug 4 [updated 2023 Apr 6]. In: Adam MP, Bick S, Mirzaa GM, et al., editors. GeneReviews. Seattle (WA): University of Washington, Seattle; 1993-2026. PMID: .
• Cross N, van Steen C, Zegaoui Y, Satherley A, Angelillo L. Retinitis pigmentosa: burden of disease and current unmet needs. Clin Ophthalmol. 2022;16:1993-2010. PMID: .