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We performed a focused evidence synthesis integrating mechanistic literature on somatic mosaicism and vascular remodeling with clinical evidence from randomized trials, observational cohorts, and quantitative-imaging studies. Key endpoints and theragnostic concepts were summarized to inform trial design and individualized treatment strategies.\u00a0Somatic activating variants in GNAQ and related signaling networks drive endothelial dysfunction, aberrant vessel maturation, and lesion progression. Pulsed-dye laser(PDL) remains the global first-line modality, but response is heterogeneous and often incomplete, particularly in thick or nodular lesions. Hematoporphyrin monomethyl ether (hemoporfin)-mediated photodynamic therapy(PDT) shows high efficacy for selected phenotypes but carries distinct adverse-event profiles. Emerging theragnostics\u2014including dynamic optical coherence tomography(D-OCT) and computational reconstruction\u2014enable noninvasive quantification of vessel depth and caliber, supporting phenotype-guided parameter selection and objective response assessment.\u00a0A mechanistically anchored, phenotype-informed framework that integrates molecular drivers with quantitative vascular imaging can accelerate precision strategies for PWS, improve endpoint rigor, and guide next-generation combination and targeted therapies.<\/jats:p>","DOI":"10.1007\/s10103-026-04957-7","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T03:44:16Z","timestamp":1784691856000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Port-wine stains: molecular drivers, translational models, and emerging theragnostic directions"],"prefix":"10.1007","volume":"41","author":[{"given":"Jing","family":"Zhou","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lu","family":"Hua","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liqiang","family":"Gan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"issue":"6","key":"4957_CR1","doi-asserted-by":"publisher","first-page":"1601","DOI":"10.1111\/bjd.15716","volume":"177","author":"W Tan","year":"2017","unstructured":"Tan W, Wang J, Zhou F et al (2017) Coexistence of Eph receptor B1 and ephrin B2 in port-wine stain endothelial progenitor cells contributes to clinicopathological vasculature dilatation. 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