{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:00:09Z","timestamp":1753891209353,"version":"3.41.2"},"reference-count":23,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T00:00:00Z","timestamp":1642377600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma\/Mitogen-activated protein kinase (RAS\/MAPK) pathway and characterized by short stature, heart defects, pectus excavatum, webbed neck, learning disabilities, cryptorchidism, and facial dysmorphia. Villonodular synovitis is a joint disorder most common in young adults characterized by an abnormal proliferation of the synovial membrane. Multifocal Villonodular synovitis is a rare disease whose recurrent nature can make its management particularly difficult. Currently, there is no systemic therapy recommended in diffuse and recurrent forms, especially because of the fear of long-term side effects in patients, who are usually young. Yet, tyrosine kinase inhibitors seem promising to reduce the effects of an aberrant colony stimulating factor-1 (CSF-1) production at the origin of the synovial nodule proliferation. We present here the case of a 21-year-old woman with NS associated to diffuse multifocal villonodular synovitis (DMVS). Our clinical case provides therapeutic experience in this very rare association. Indeed, in association with surgery, the patient improved considerably: she had complete daily life autonomy, knee joint amplitudes of 100\u00b0 in flexion and 0\u00b0 in extension and was able to walk for 10 min without any technical assistance. To our knowledge, this is the first case of a patient suffering from DMVS associated with a Noonan syndrome treated with Glivec<jats:sup>\u00ae<\/jats:sup>(oral administration at a dosage of 340 mg\/m<jats:sup>2<\/jats:sup>in children, until disease regression) on a long-term basis.<\/jats:p>","DOI":"10.3389\/fmed.2021.817873","type":"journal-article","created":{"date-parts":[[2022,1,17]],"date-time":"2022-01-17T04:38:47Z","timestamp":1642394327000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Imatinib, a New Adjuvant Medical Treatment for Multifocal Villonodular Synovitis Associated to Noonan Syndrome: A Case Report and Literature Review"],"prefix":"10.3389","volume":"8","author":[{"given":"Romain","family":"Dalla-Torre","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vincent","family":"Crenn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Menu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bertrand","family":"Isidor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pascale","family":"Guillot","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benoit","family":"Le Goff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Loic","family":"Geffroy","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Dauty","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alban","family":"Fouasson-Chailloux","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,1,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1097\/00003086-200105000-00025","article-title":"Pigmented villonodular synovitis: keys to early diagnosis","volume":"386","author":"Bhimani","year":"2001","journal-title":"Clin Orthop Relat Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1007\/s11864-015-0385-x","article-title":"Current systemic treatment options for tenosynovial giant cell tumor\/pigmented villonodular synovitis: targeting the CSF1\/CSF1R axis","volume":"17","author":"Brahmi","year":"2016","journal-title":"Curr Treat Options Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1001\/archpedi.1968.02100020377005","article-title":"Hypertelorism with Turner phenotype. A new syndrome with associated congenital heart disease","volume":"116","author":"Noonan","year":"1968","journal-title":"Am J Dis Child."},{"key":"B4","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1136\/jmg.24.1.9","article-title":"Noonan syndrome","volume":"24","author":"Allanson","year":"1987","journal-title":"J Med Genet."},{"key":"B5","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/ejhg.2008.188","article-title":"Multiple giant cell lesions in patients with Noonan syndrome and cardio-facio-cutaneous syndrome","volume":"17","author":"Neumann","year":"2009","journal-title":"Eur J Hum Genet."},{"key":"B6","doi-asserted-by":"publisher","first-page":"105270","DOI":"10.1016\/j.jbspin.2021.105270","article-title":"Joint involvement in Noonan syndrome. A retrospective paediatric descriptive study","volume":"89","author":"Le Quellec","year":"2021","journal-title":"Joint Bone Spine."},{"key":"B7","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1002\/ajmg.1320400208","article-title":"Noonan-like\/multiple giant cell lesion syndrome","volume":"40","author":"Cohen","year":"1991","journal-title":"Am J Med Genet."},{"key":"B8","doi-asserted-by":"publisher","first-page":"e1547","DOI":"10.1016\/j.eats.2017.06.029","article-title":"Systematic arthroscopic treatment of diffuse pigmented villonodular synovitis in the knee","volume":"6","author":"Chang","year":"2017","journal-title":"Arthrosc Tech."},{"key":"B9","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1302\/0301-620X.97B4.34907","article-title":"The effect of surgical synovectomy and radiotherapy on the rate of recurrence of pigmented villonodular synovitis of the knee: an individual patient meta-analysis","author":"Mollon","year":"2015","journal-title":"Bone Joint J."},{"key":"B10","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1038\/jhg.2013.118","article-title":"A new mutation in the C-SH2 domain of PTPN11 causes Noonan syndrome with multiple giant cell lesions","volume":"59","author":"Carapito","year":"2014","journal-title":"J Hum Genet."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2966","DOI":"10.1002\/ajmg.a.32538","article-title":"Pigmented villonodular synovitis in a patient with Noonan syndrome and SOS1 gene mutation","author":"Mascheroni","year":"2008","journal-title":"Am J Med Genet A."},{"key":"B12","doi-asserted-by":"publisher","first-page":"14551","DOI":"10.1038\/s41598-019-51211-y","article-title":"Long-term efficacy of imatinib mesylate in patients with advanced tenosynovial giant cell tumor","volume":"9","author":"Verspoor","year":"2019","journal-title":"Sci Rep."},{"key":"B13","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/S0140-6736(19)30764-0","article-title":"Pexidartinib versus placebo for advanced tenosynovial giant cell tumour (ENLIVEN): a randomised phase 3 trial","volume":"394","author":"Tap","year":"2019","journal-title":"Lancet."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1216","DOI":"10.1038\/ejhg.2009.44","article-title":"SOS1 and PTPN11 mutations in five cases of Noonan syndrome with multiple giant cell lesions","volume":"17","author":"Beneteau","year":"2009","journal-title":"Eur J Hum Genet."},{"key":"B15","doi-asserted-by":"crossref","first-page":"392","DOI":"10.55095\/achot2008\/070","article-title":"Polyarticular form of pigmented villonodular synovitis. Radiation and surgical therapy: long term follow-up","volume":"75","author":"Vavr\u00edk","year":"2008","journal-title":"Acta Chir Orthop Traumatol Cech."},{"key":"B16","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s00247-016-3743-3","article-title":"Multifocal tenosynovial giant cell tumors in a child with Noonan syndrome","volume":"47","author":"Meyers","year":"2017","journal-title":"Pediatr Radiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"7698052","DOI":"10.1155\/2018\/7698052","article-title":"Multifocal pigmented villonodular synovitis in the noonan syndrome","volume":"2018","author":"Miri","year":"2018","journal-title":"Case Rep Orthop."},{"key":"B18","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1093\/annonc\/mdn033","article-title":"Complete response to imatinib in relapsing pigmented villonodular synovitis\/tenosynovial giant cell tumor (PVNS\/TGCT)","volume":"19","author":"Blay","year":"2008","journal-title":"Ann Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1080\/08998280.2011.11928700","article-title":"Pigmented villonodular synovitis responsive to imatinib therapy","volume":"24","author":"Snoots","year":"2011","journal-title":"Proc (Bayl Univ Med Cent)."},{"key":"B20","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1186\/2045-3329-3-8","article-title":"Response to imatinib in villonodular pigmented synovitis (PVNS) resistant to nilotinib","volume":"3","author":"Stacchiotti","year":"2013","journal-title":"Clin Sarcoma Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1649","DOI":"10.1002\/cncr.26409","article-title":"Efficacy of imatinib mesylate for the treatment of locally advanced and\/or metastatic tenosynovial giant cell tumor\/pigmented villonodular synovitis","volume":"118","author":"Cassier","year":"2012","journal-title":"Cancer."},{"key":"B22","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.suronc.2020.08.030","article-title":"J. The effect of imatinib mesylate in diffuse-type tenosynovial giant cell tumours on MR imaging and PET-CT","volume":"35","author":"Mastboom","year":"2020","journal-title":"Surg Oncol."},{"key":"B23","doi-asserted-by":"publisher","first-page":"e0233046","DOI":"10.1371\/journal.pone.0233046","article-title":"Long term term follow-up of tyrosine kinase inhibitors treatments in inoperable or relapsing diffuse type tenosynovial giant cell tumors (dTGCT)","volume":"15","author":"Brahmi","year":"2020","journal-title":"PLoS ONE."}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.817873\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,11,15]],"date-time":"2023-11-15T22:09:51Z","timestamp":1700086191000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2021.817873\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,1,17]]},"references-count":23,"alternative-id":["10.3389\/fmed.2021.817873"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2021.817873","relation":{},"ISSN":["2296-858X"],"issn-type":[{"type":"electronic","value":"2296-858X"}],"subject":[],"published":{"date-parts":[[2022,1,17]]},"article-number":"817873"}}