{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T07:41:37Z","timestamp":1791013297317,"version":"4.1.0"},"reference-count":47,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T00:00:00Z","timestamp":1497830400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["Grant HG200388\u201003"],"award-info":[{"award-number":["Grant HG200388\u201003"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,9]]},"abstract":"<jats:sec><jats:label\/><jats:p>Patients with overgrowth and complex vascular malformation syndromes, including Proteus syndrome have an increased risk of thromboembolism. Proteus syndrome is a mosaic, progressive overgrowth disorder involving vasculature, skin, and skeleton, and caused by a somatic activating mutation in <jats:italic>AKT1<\/jats:italic>. We conducted a comprehensive review of the medical histories and hematologic evaluations of 57 patients with Proteus syndrome to identify potential risk factors for thrombosis. We found that six of ten patients, who were deceased, died secondary to deep venous thrombosis and\/or pulmonary embolism. Of the remaining 47 living patients, six had thromboembolic events that all occurred postoperatively and in an affected limb. Eleven of 21 patients had an abnormal hypercoagulable panel including Factor V Leiden heterozygotes, antithrombin III deficiency, positive lupus anticoagulant, or Protein C or S deficiencies. We observed that eight of 17 patients had an abnormal D\u2010dimer level &gt;0.5\u2009mcg\/dl, but deep venous thromboses occurred in only four of those with D\u2010dimer &gt;1.0\u2009mcg\/dl. We conclude that the predisposition to thrombosis is likely to be multifaceted with risk factors including vascular malformations, immobility, surgery, additional prothrombotic factors, and possible pathophysiologic effects of the somatic <jats:italic>AKT1<\/jats:italic> mutation on platelet function or the vascular endothelium. The D\u2010dimer test is useful as a screen for thromboembolism, although the screening threshold may need to be adjusted for patients with this disorder. We propose developing a registry to collect D\u2010dimer and outcome data to facilitate adjustment of the D\u2010dimer threshold for Proteus syndrome and related disorders, including PIK3CA\u2010Related Overgrowth Spectrum.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38311","type":"journal-article","created":{"date-parts":[[2017,6,19]],"date-time":"2017-06-19T05:32:46Z","timestamp":1497850366000},"page":"2359-2365","source":"Crossref","is-referenced-by-count":35,"title":["Characterization of thrombosis in patients with Proteus syndrome"],"prefix":"10.1002","volume":"173","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8250-164X","authenticated-orcid":false,"given":"Kim M.","family":"Keppler\u2010Noreuil","sequence":"first","affiliation":[{"name":"Medical Genomics Metabolic Genetics Branch, National Human Genome Research Institute National Institutes of Health Bethesda Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jay 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