Diagnostic Value of Congenital Hypertrophy of the Retinal Pigment Epithelium in Familial Adenomatous Polyposis: A Systematic Review Publisher



Asadi Khameneh E ; Dadkhah R ; Zangiabadian M ; Mafi A ; Hashemi A ; Sanei M ; Mirshahi A ; Mahdizad Z ; Bazvand F
Source: International Journal of Retina and Vitreous Published:2026

Abstract

Background: Congenital hypertrophy of the retinal pigment epithelium (CHRPE) has been proposed as a phenotypic marker of familial adenomatous polyposis (FAP). This systematic review aimed to evaluate the evidence regarding the association between CHRPE and FAP and to determine the potential clinical utility of CHRPE for the early identification of individuals with adenomatous polyposis coli (APC) mutations. Methods: A systematic search of PubMed/MEDLINE, Embase, and Web of Science from inception to August 2025 in accordance with PRISMA guideline and a PROSPERO-registered protocol was done. Studies reporting CHRPE in individuals with confirmed or suspected FAP or at-risk first-degree relatives were identified. Data extraction and quality assessment using Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool were performed independently by two reviewers. Due to substantial heterogeneity in CHRPE definitions, diagnostic criteria, population characteristics, and APC mutation testing methods, quantitative pooling was not considered appropriate and findings were synthesized qualitatively. Results: Forty-three studies were included. CHRPE demonstrated consistently high specificity for FAP and APC mutation carriage across most studies. Sensitivity ranged from 40% to 100% in affected individuals and from 57% to 100% in at-risk relatives, while specificity ranged from 58% to 100%, depending on diagnostic criteria. Stricter definitions incorporating lesion multiplicity and bilaterality improved specificity at the expense of sensitivity. Conclusion: CHRPE is associated with FAP but demonstrates variable diagnostic performance across studies. Its clinical utility as a standalone screening marker is limited by heterogeneous diagnostic definitions. Standardized diagnostic criteria and prospective studies using contemporary genetic testing are needed. © The Author(s) 2026.