{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T22:36:07Z","timestamp":1790807767154,"version":"4.1.0"},"reference-count":27,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,6]],"date-time":"2021-12-06T00:00:00Z","timestamp":1638748800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100008530","name":"European Regional Development Fund","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100008530","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI17\/00519"],"award-info":[{"award-number":["FIS PI17\/00519"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"publisher","award":["FIS PI20\/1053"],"award-info":[{"award-number":["FIS PI20\/1053"]}],"id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Genetics"],"published-print":{"date-parts":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Segmental overgrowth has been widely described in patients with congenital vascular anomalies. However, segmental undergrowth has been poorly characterized, and no large series of patients have been published. We present the clinical and molecular characteristics a cohort of 37 patients with vascular malformations and segmental undergrowth. True undergrowth was only considered when the musculoskeletal system was involved to avoid confusion with other causes of segmental reduction, as in lipodystrophy or the long\u2010term osteopenia seen in patients with Servelle\u2013Martorell syndrome. Deep high\u2010throughput sequencing was performed in tissue samples from 20 patients using a custom panel. We identified three groups: undergrowth associated with (1) venous, (2) capillary\u2010venous, and (3) lymphatic\u2010capillary\u2010venous malformations. Congenital or early childhood onset undergrowth can occur with or without associated overgrowth. Different likely pathogenic or pathogenic variants were detected in 13 of 20 (65%) tissue samples in the\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    ,\n                    <jats:italic>TEK<\/jats:italic>\n                    ,\n                    <jats:italic>GNAQ<\/jats:italic>\n                    , or\n                    <jats:italic>GNA11<\/jats:italic>\n                    genes. In conclusion, the eponymous Servelle\u2013Martorell syndrome should not be used as a synonym for undergrowth. Segmental undergrowth should be considered a characteristic associated with vascular malformations. Patients with\n                    <jats:italic>PIK3CA<\/jats:italic>\n                    variants show all different combinations of overgrowth and undergrowth. Thus, the term PROS (PIK3CA\u2010related overgrowth spectrum) does not cover the entire spectrum.\n                  <\/jats:p>","DOI":"10.1111\/cge.14095","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T03:03:54Z","timestamp":1638327834000},"page":"296-306","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Segmental undergrowth is associated with pathogenic variants in vascular malformation genes: A retrospective case\u2010series study"],"prefix":"10.1111","volume":"101","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4680-881X","authenticated-orcid":false,"given":"Victor","family":"Martinez\u2010Glez","sequence":"first","affiliation":[{"name":"Vascular Malformations Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"},{"name":"Clinical Genetics Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, ISCIII  Madrid Spain"},{"name":"Ithaca, European Reference Network, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara","family":"Rodriguez\u2010Laguna","sequence":"additional","affiliation":[{"name":"Vascular Malformations Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanesa","family":"Viana\u2010Huete","sequence":"additional","affiliation":[{"name":"Vascular Malformations Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolina","family":"Garc\u00eda Torrijos","sequence":"additional","affiliation":[{"name":"Vascular Malformations Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bego\u00f1a","family":"Hurtado","sequence":"additional","affiliation":[{"name":"Vascular Malformations Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pablo","family":"Lapunzina","sequence":"additional","affiliation":[{"name":"Clinical Genetics Section Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"},{"name":"CIBERER, Centro de Investigaci\u00f3n Biom\u00e9dica en Red de Enfermedades Raras, ISCIII  Madrid Spain"},{"name":"Ithaca, European Reference Network, Hospital Universitario La Paz  Madrid Spain"},{"name":"Overgrowth Syndromes Laboratory Institute of Medical and Molecular Genetics, INGEMM\u2010IdiPAZ, Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paloma","family":"Triana","sequence":"additional","affiliation":[{"name":"Vascular Anomalies Unit, Department of Pediatric Surgery Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"L\u00f3pez\u2010Guti\u00e9rrez","sequence":"additional","affiliation":[{"name":"Vascular Anomalies Unit, Department of Pediatric Surgery Hospital Universitario La Paz  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,12,6]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/gim.2016.220"},{"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":"10.1056\/NEJMoa1104017"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1086\/379793"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2013.05.030"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.23736\/S0392-9590.19.04154-3"},{"key":"e_1_2_11_8_1","first-page":"1","article-title":"Hemangiomatosis braquial osteolitica","volume":"1","author":"Martorell F","year":"1949","journal-title":"Angiologia"},{"key":"e_1_2_11_9_1","first-page":"436","article-title":"Des angiomes veineux (about venous angiomas)","volume":"41","author":"Servelle MT","year":"1948","journal-title":"Arch 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