{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,30]],"date-time":"2026-05-30T07:01:14Z","timestamp":1780124474398,"version":"3.54.0"},"reference-count":38,"publisher":"Springer Science and Business Media LLC","issue":"5","license":[{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T00:00:00Z","timestamp":1777680000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005378","name":"Hacettepe University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005378","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Eur J Pediatr"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Fibrodysplasia ossificans progressiva (FOP) is a rare multisystem disorder with the triad of congenital hallux valgus, flare-ups and progressive heterotopic ossification. The flare-ups (episodes of painful soft-tissue swelling) start in early childhood, and progress to ossification with cumulative functional disability. We describe the cohort of FOP from a single tertiary center in T\u00fcrkiye and highlight the phenotypic variabilities and diagnostic pitfalls. The subjects included 10 affected individuals (7 females and 3 males, aged 10\u00a0days to 20\u00a0years), whose diagnosis was confirmed with molecular tests, including full\n                    <jats:italic>ACVR1<\/jats:italic>\n                    sequencing, targeted hotspot analysis, a gene panel for skeletal disorders, and whole-exome sequencing. Clinical and imaging data were retrospectively reviewed. The common pathogenic variant of FOP, c.617G\u2009&gt;\u2009A, p.(Arg206His) of\n                    <jats:italic>ACVR1<\/jats:italic>\n                    , was found in 9 patients, while a rare variant, c.983G\u2009&gt;\u2009A, p.(Gly328Glu) in one. All patients with the common variant exhibited the classical triad of FOP. Other morbidities included limited cervical mobility in 8, temporomandibular joint involvement in 4, scoliosis in 6, scalp nodules in 6, and brain anomalies in 2. Scalp nodules could be a transient finding with spontaneous regression and were an early manifestation in 2. One patient showed a distinctive brain malformation of FOP (pontine dysmorphism with fusion of the facial colliculi and dorsal bulging into the fourth ventricle). Four patients underwent biopsy prior to referral to our institution. One was coincidentally associated with Ewing sarcoma. The infant with the rare variant presented with limb reduction defects and brain malformation and had not yet developed flare-ups or heterotopic ossification.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:italic>Conclusion<\/jats:italic>\n                    : This single-center cohort from T\u00fcrkiye confirms the key clinical features of FOP associated with both common and rare\n                    <jats:italic>ACVR1<\/jats:italic>\n                    variants and expands the radiological findings with notable features such as pontine malformation. It also highlights scalp nodules as a potential early diagnostic clue, emphasizing the importance of early clinical recognition and timely molecular confirmation, while providing insights that may inform future therapeutic approaches.\n                    <jats:table-wrap>\n                      <jats:table>\n                        <jats:tbody>\n                          <jats:tr>\n                            <jats:td colspan=\"2\">\n                              <jats:bold>What Is Known:<\/jats:bold>\n                              <jats:italic>\u2022 Fibrodysplasia ossificans progressiva (FOP) is caused by activating variants in ACVR1, most commonly c.617GA, p.(Arg206His), and is characterized by congenital hallux valgus, flare-ups, and progressive heterotopic ossification<\/jats:italic>\n                              <jats:italic>\u2022 Early diagnosis is challenging, and misdiagnosis may lead to harmful invasive procedures such as biopsies.<\/jats:italic>\n                              <jats:bold>What Is New:<\/jats:bold>\n                              <jats:italic>\u2022 This single-center cohort confirms the key features of FOP, expands the radiological spectrum (including pontine malformation), and identifies scalp nodules as an early diagnostic clue.<\/jats:italic>\n                            <\/jats:td>\n                          <\/jats:tr>\n                        <\/jats:tbody>\n                      <\/jats:table>\n                    <\/jats:table-wrap>\n                  <\/jats:p>","DOI":"10.1007\/s00431-026-06974-8","type":"journal-article","created":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T14:10:27Z","timestamp":1777731027000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Fibrodysplasia ossificans progressiva in children: diagnostic pitfalls and ACVR1 genotype\u2013phenotype spectrum"],"prefix":"10.1007","volume":"185","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0843-5370","authenticated-orcid":false,"given":"Nazli Busra","family":"Acikgoz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3370-5261","authenticated-orcid":false,"given":"Burcu","family":"Senkalfa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5945-286X","authenticated-orcid":false,"given":"Berna","family":"Celik Ertas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1968-5527","authenticated-orcid":false,"given":"Zulal","family":"Ozdemir Uslu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-7664-815X","authenticated-orcid":false,"given":"Ekim","family":"Helhel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9928-3236","authenticated-orcid":false,"given":"Gizem","family":"Urel Demir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0683-9731","authenticated-orcid":false,"given":"Yasemin","family":"Alanay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7208-8097","authenticated-orcid":false,"given":"Adalet Elcin","family":"Yildiz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6577-5542","authenticated-orcid":false,"given":"Gulen Eda","family":"Utine","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2390-5123","authenticated-orcid":false,"given":"Z. Alev","family":"Ozon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7244-7766","authenticated-orcid":false,"given":"Pelin Ozlem","family":"Simsek Kiper","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,5,2]]},"reference":[{"key":"6974_CR1","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1385\/BMM:3:3-4:183","volume":"3","author":"FS Kaplan","year":"2005","unstructured":"Kaplan FS et al (2005) The phenotype of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab 3:183\u2013188","journal-title":"Clin Rev Bone Miner Metab"},{"key":"6974_CR2","unstructured":"Akesson LS, S.R.F.O.P.J.U.M.I.A.M., Feldman J, Mirzaa GM, et al (2020) editors. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 1993\u20132025. 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