{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T20:07:11Z","timestamp":1789589231992,"version":"build-2803163510"},"reference-count":12,"publisher":"Cold Spring Harbor Laboratory","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cold Spring Harb Mol Case Stud"],"published-print":{"date-parts":[[2021,12]]},"abstract":"\n Disorganized morphogenesis of arteries, veins, capillaries, and lymphatic vessels results in vascular malformations. Most individuals with isolated vascular malformations have postzygotic (mosaic), activating pathogenic variants in a handful of oncogenes within the PI3K\u2013RAS\u2013MAPK pathway (Padia et al.,\n Laryngoscope Investig Otolaryngol<\/jats:italic>\n 4: 170\u2013173 [2019]). Activating pathogenic variants in the gene\n PIK3CA<\/jats:italic>\n , which encodes for the catalytic subunit of phosphatidylinositol 3-kinase, are present in both lymphatic and venous malformations as well as arteriovenous malformations in other complex disorders such as CLOVES syndrome (congenital, lipomatous, overgrowth, vascular malformations, epidermal anevi, scoliosis) (Luks et al.,\n Pediatr Dev Pathol<\/jats:italic>\n 16: 51 [2013]; Luks et al.,\n J Pediatr<\/jats:italic>\n 166: 1048\u20131054.e1\u20135 [2015]; Al-Olabi et al.,\n J Clin Invest<\/jats:italic>\n 128: 1496\u20131508 [2018]). These vascular malformations are part of the\n PIK3CA<\/jats:italic>\n -related overgrowth spectrum, a spectrum of entities that have regionalized disordered growth due to the presence of tissue-restricted postzygotic\n PIK3CA<\/jats:italic>\n pathogenic variants (Keppler-Noreuil et al.,\n Am J Med Genet A<\/jats:italic>\n 167A: 287\u2013295 [2015]). Cerebrofacial vascular metameric syndrome (CVMS; also described as cerebrofacial arteriovenous metameric syndrome, Bonnet\u2013Dechaume\u2013Blanc syndrome, and Wyburn\u2013Mason syndrome) is the association of retinal, facial, and cerebral vascular malformations (Bhattacharya et al.,\n Interv Neuroradiol<\/jats:italic>\n 7: 5\u201317 [2001]; Krings et al.,\n Neuroimaging Clin N Am<\/jats:italic>\n 17: 245\u2013258 [2007]). The segmental distribution, the presence of tissue overgrowth, and the absence of familial recurrence are all consistent with CVMS being caused by a postzygotic mutation, which has been hypothesized by previous authors (Brinjiki et al.,\n Am J Neuroradiol<\/jats:italic>\n 39: 2103\u20132107 [2018]). However, the genetic cause of CVMS has not yet been described. Here, we present three individuals with CVMS and mosaic activating pathogenic variants within the gene\n PIK3CA<\/jats:italic>\n . We propose that CVMS be recognized as part of the\n PIK3CA<\/jats:italic>\n -related overgrowth spectrum, providing justification for future trials using pharmacologic PIK3CA inhibitors (e.g., alpelisib) for these difficult-to-treat patients.\n <\/jats:p>","DOI":"10.1101\/mcs.a006147","type":"journal-article","created":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T13:21:01Z","timestamp":1639056061000},"page":"a006147","source":"Crossref","is-referenced-by-count":11,"title":["Cerebrofacial vascular metameric syndrome is caused by somatic pathogenic variants in\n PIK3CA<\/i>"],"prefix":"10.1101","volume":"7","author":[{"given":"Sarah E.","family":"Sheppard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria R.","family":"Sanders","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abhay","family":"Srinivasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura S.","family":"Finn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise","family":"Adams","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Elton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Amlie-Lefond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zoe","family":"Nelson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria","family":"Dmyterko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Jensen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaitlyn","family":"Zenner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan","family":"Perkins","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2843-5594","authenticated-orcid":false,"given":"James T.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2021,12,9]]},"reference":[{"key":"2021120910200924000_7.6.a006147.1","doi-asserted-by":"publisher","DOI":"10.1097\/00006123-199901000-00020"},{"key":"2021120910200924000_7.6.a006147.2","doi-asserted-by":"publisher","DOI":"10.1177\/159101990100700101"},{"key":"2021120910200924000_7.6.a006147.3","doi-asserted-by":"publisher","DOI":"10.3174\/ajnr.A5811"},{"key":"2021120910200924000_7.6.a006147.4","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-15-1654"},{"key":"2021120910200924000_7.6.a006147.5","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab117"},{"key":"2021120910200924000_7.6.a006147.6","doi-asserted-by":"publisher","DOI":"10.1016\/j.nic.2007.02.006"},{"key":"2021120910200924000_7.6.a006147.7","doi-asserted-by":"publisher","DOI":"10.1016\/j.jid.2016.06.204"},{"key":"2021120910200924000_7.6.a006147.8","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.87623"},{"key":"2021120910200924000_7.6.a006147.9","doi-asserted-by":"publisher","DOI":"10.3171\/jns.1997.87.2.0190"},{"key":"2021120910200924000_7.6.a006147.10","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-021-03562-8"},{"key":"2021120910200924000_7.6.a006147.11","doi-asserted-by":"publisher","DOI":"10.1172\/jci.insight.129884"},{"key":"2021120910200924000_7.6.a006147.12","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-020-00943-8"}],"container-title":["Molecular Case Studies"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/mcs.a006147","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,12,9]],"date-time":"2021-12-09T13:21:17Z","timestamp":1639056077000},"score":1,"resource":{"primary":{"URL":"http:\/\/molecularcasestudies.cshlp.org\/lookup\/doi\/10.1101\/mcs.a006147"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12]]},"references-count":12,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2021,12,9]]},"published-print":{"date-parts":[[2021,12]]}},"alternative-id":["10.1101\/mcs.a006147"],"URL":"https:\/\/doi.org\/10.1101\/mcs.a006147","relation":{},"ISSN":["2373-2865","2373-2873"],"issn-type":[{"value":"2373-2865","type":"print"},{"value":"2373-2873","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12]]}}}