Clinical Spectrum of Germline Pathogenic Variants in RASA1 and EPHB4 : Systematic review v1

Résumé fourni par la source

Background Germline pathogenic variants inRASA1andEPHB4are associated with a broad spectrum of vascular and lymphatic disorders, including capillary malformation–arteriovenous malformation syndrome, Parkes Weber syndrome, hereditary hemorrhagic telangiectasia–associated manifestations, central conducting lymphatic anomalies, and nonimmune hydrops fetalis. However, the overall phenotypic spectrum remains incompletely characterized. Objective This systematic review aims to comprehensively characterize the clinical spectrum associated with germline pathogenic or likely pathogenic variants inRASA1andEPHB4and to explore potential genotype–phenotype associations. Methods PubMed/MEDLINE, Embase, and the Cochrane Library will be searched for studies published from 2000 to August 2026. Studies reporting sufficiently detailed clinical data from genetically confirmed variant carriers will be included. Data will be extracted using a standardized form, with AI-assisted initial extraction followed by systematic human verification. Potentially overlapping reports will be reconciled, phenotypic features will be coded as present, absent, or not reported, and methodological quality will be assessed using JBI tools. Findings will be synthesized descriptively, with exploratory statistical analyses when appropriate. Conclusion This review aims to provide an integrated view ofRASA1- andEPHB4-related disorders and clarify their vascular and lymphatic phenotypic overlap.

Ce résumé expose les affirmations des auteurs. BNTIC ne l’interprète pas comme une validation indépendante des résultats.