{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T14:56:05Z","timestamp":1791384965336,"version":"4.3.3"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2016,8,3]],"date-time":"2016-08-03T00:00:00Z","timestamp":1470182400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2017,1]]},"abstract":"<jats:p>Overgrowth syndromes are characterized by global or localized disproportionate growth associated with other anomalies, including vascular malformations and neurological and\/or visceral disorders. <jats:styled-content style=\"fixed-case\">CLOVES<\/jats:styled-content> (Congenital Lipomatous asymmetric Overgrowth of the trunk with lymphatic, capillary, venous, and combined\u2010type Vascular malformations, Epidermal naevi, Scoliosis\/Skeletal and spinal anomalies) is an overgrowth syndrome caused by mosaic activating mutation in gene <jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content>, which gives rise to abnormal <jats:styled-content style=\"fixed-case\">PI3K\u2010AKT\u2010mTOR<\/jats:styled-content> pathway activation. These mutations are responsible for the clinical manifestations of the syndrome, which include low\u2010 and high\u2010flow vascular malformations, thoracic lipomatous hyperplasia, asymmetric growth, and visceral and neurological disorders. These common anomalies are illustrated with figures from two personal cases. Identification of the clinical and genetic characteristics of <jats:styled-content style=\"fixed-case\">CLOVES<\/jats:styled-content> syndrome is crucial for the differential diagnosis with other overgrowth syndromes, such as Proteus or Klippel\u2013Trenaunay (K\u2013T) syndromes, and for the therapeutic management of the different anomalies. In this context, a new entity comprising different syndromes with phenotypic mutations in <jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content> has been proposed, designated <jats:styled-content style=\"fixed-case\">PIK3CA<\/jats:styled-content>\u2010related overgrowth spectrum (<jats:styled-content style=\"fixed-case\">PROS<\/jats:styled-content>), with the aim of facilitating clinical management and establishing appropriate genetic study criteria.<\/jats:p>","DOI":"10.1111\/cge.12832","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T10:17:19Z","timestamp":1468837039000},"page":"14-21","source":"Crossref","is-referenced-by-count":132,"title":["<scp>CLOVES<\/scp> syndrome: review of a <scp>PIK3CA<\/scp>\u2010related overgrowth spectrum (<scp>PROS<\/scp>)"],"prefix":"10.1111","volume":"91","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0304-7317","authenticated-orcid":false,"given":"A.","family":"Martinez\u2010Lopez","sequence":"first","affiliation":[{"name":"Dermatology Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G.","family":"Blasco\u2010Morente","sequence":"additional","affiliation":[{"name":"Dermatology Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"I.","family":"Perez\u2010Lopez","sequence":"additional","affiliation":[{"name":"Dermatology Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.D.","family":"Herrera\u2010Garcia","sequence":"additional","affiliation":[{"name":"Neurological Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M.","family":"Luque\u2010Valenzuela","sequence":"additional","affiliation":[{"name":"Orthopedical Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"D.","family":"Sanchez\u2010Cano","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.C.","family":"Lopez\u2010Gutierrez","sequence":"additional","affiliation":[{"name":"Vascular Malformations Unit Hospital Infantil La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R.","family":"Ruiz\u2010Villaverde","sequence":"additional","affiliation":[{"name":"Dermatology Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Tercedor\u2010Sanchez","sequence":"additional","affiliation":[{"name":"Dermatology Unit Complejo Hospitalario Universitario  Granada Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2016,8,3]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31362"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36836"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0036-1571792"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng.2332"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.05.006"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36672"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annder.2014.04.119"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1104017"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.spen.2015.11.001"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2014-3673"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13147"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00247-010-1559-0"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.sempedsurg.2014.07.003"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1148\/rg.331125052"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coms.2015.07.006"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2010.01149.x"},{"issue":"25","key":"e_1_2_11_18_1","first-page":"31","article-title":"The group of epidermal nevus syndromes Part II. 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