Author: Divya Narayanan (United States)
Co-authors: Chris Simpson, Cathy Lally
Purpose
X-linked retinitis pigmentosa (XLRP) is a rare, X-linked inherited retinal dystrophy that predominantly affects males. XLRP initially presents as night blindness in childhood and early adolescence, followed by reduction of the visual field. In advanced XLRP, profound central vision loss and legal blindness can occur. The phenotype of XLRP can vary, generally presenting as a more severe form of retinitis pigmentosa (RP). XLRP is associated with different genetic mutations, of which RPGR accounts for a majority of XLRP cases. Although several potential treatment strategies for XLRP are being investigated, there are currently no approved disease-modifying therapies. The objective of this study was to determine the prevalence specifically for RPGR-mutated XLRP among males in Europe and the United States (US).
Setting/Venue
A comprehensive literature review was conducted on the basis of a broad search of PubMed and EMBASE databases.
Methods
Published literature related to RP prevalence, XLRP prevalence, classification of inheritance types, misdiagnosis, and RPGR mutation occurrence was reviewed. English-language studies from Europe and the US were screened for inclusion. For studies of prevalence and proportions of inheritance types, only studies of male populations were included. To estimate the prevalence of RPGR-mutated XLRP among males, four components were estimated: (1) the prevalence of nonsyndromic RP in males; (2) the proportion of RP in males that is X-linked; (3) the proportion of male RP cases for whom the presumed pattern of inheritance is reclassified as X-linked after genotyping; and (4) the proportion of XLRP that is RPGR-mutated XLRP. Individual estimates of these components were extracted from the studies identified in the literature review and, for each component, a sample size–weighted average of the individual study-level estimates was calculated. The prevalence of RPGR-mutated XLRP among males was estimated by multiplying components 1 and 2, factoring in misclassification using component 3, and then multiplying by component 4. In a parallel analysis of studies that provided a direct estimate of XLRP prevalence among males, a weighted average was corrected per reclassification analysis of X-linked cases (component 3) and multiplied by component 4.
Results
Two studies assessed the prevalence of XLRP directly among males, one from Denmark (3.8/100,000 males) and one from the US (2.3/100,000 males); median prevalence was 3.1/100,000 males and weighted average was 3.5/100,000 males. To indirectly measure the prevalence of XLRP, studies estimating the prevalence of RP among males and studies estimating the proportion of XLRP inheritance among RP cases were examined. Seven studies reported the prevalence of nonsyndromic RP among males in the US and Europe (range: 12.2-28.0/100,000 males; median: 21.5/100,000 males; weighted average: 19.6/100,000 males). Seven studies from the US and Europe reported on the proportion of RP cases classified as X-linked among males (range: 4.0%-21.2%; median: 10.4%; weighted average: 14.0%). Together, these estimates indirectly provided a prevalence estimate of approximately 2.7/100,000 males. The proportion of RP cases reclassified as X-linked from other inheritance types (simplex or autosomal dominant) was estimated, resulting in a corrected prevalence of XLRP of 4.0/100,000 males for the indirect estimate and 5.2/100,000 males for the direct estimate. Lastly, the proportion of RPGR-mutated XLRP was assessed from the literature (range: 74.7%-91.9%; median: 85.7%; weighted average: 84.1%). Applying this proportion to the prevalence of XLRP yielded an overall prevalence of 3.4-4.4/100,000 males with RPGR-mutated XLRP.
Conlusions
The prevalence of RPGR-mutated XLRP is estimated to be 3.4-4.4/100,000 males in Europe and the US. This number was adjusted for misclassification of RP cases as X-linked from autosomal dominant or simplex inheritance. Among XLRP cases, the majority were due to mutations in the RPGR gene. These findings address an important gap in the understanding of RPGR-mutated XLRP by providing additional clarity around the prevalence of this rare condition. This information may help medical institutions, physicians, and other stakeholders in the health care system support people living with this inherited retinal disease.
Financial Disclosure
LCV-I: Biogen (employee and may hold stock or stock options in the company). CS and CL have nothing to disclose. This study was supported by Biogen. Medical writing and editorial assistance were provided by MedThink SciCom, Cary, NC, USA, and funded by Biogen.
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