{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:52:17Z","timestamp":1787320337702,"version":"build-2736575974"},"reference-count":17,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T00:00:00Z","timestamp":1762128000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100008484","name":"BioMarin Pharmaceutical","doi-asserted-by":"publisher","award":["BioMarin Pharmaceutical"],"award-info":[{"award-number":["BioMarin Pharmaceutical"]}],"id":[{"id":"10.13039\/100008484","id-type":"DOI","asserted-by":"publisher"}]},{"name":"French Ministry of Health","award":["French Ministry of Health"],"award-info":[{"award-number":["French Ministry of Health"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Orphanet J Rare Dis"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Achondroplasia (ACH) and hypochondroplasia (HCH) are among the most common forms of skeletal dysplasia, caused by gain-of-function variants in the\n                      <jats:italic>FGFR3<\/jats:italic>\n                      gene, leading to disproportionate short stature. The birth prevalence of HCH remains poorly defined. In addition, the reported birth prevalence of ACH in Europe and globally may not be applicable to France, given its relatively high rate of pregnancy terminations for medical reasons. This retrospective study provides the first birth prevalence estimates for ACH and HCH in France, using the French National Registry of Rare Diseases (\n                      <jats:italic>Banque Nationale de Donn\u00e9es Maladies Rares<\/jats:italic>\n                      , BNDMR).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      As of January 2024, 766 patients with ACH (ORPHA:15) and 408 with HCH (ORPHA:429) were identified. Most patients were diagnosed and cared for within the network of constitutional bone diseases centers (ACH: 71.3%; HCH: 63.4%). Overall, 85.5% of ACH cases and 57.2% of HCH cases were related to\n                      <jats:italic>de novo<\/jats:italic>\n                      genetic variants (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). ACH was diagnosed prenatally in 40.8% and at birth in 40.6% of patients, whereas HCH was diagnosed postnatally in 65.7% of cases (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.0001). To estimate live birth prevalence, we focused on pediatric patients (0\u201315 years) born between 2008 and 2023. The mean (range) live birth prevalence was 3.27 per 100,000 for ACH (1.90\u20134.03) and 1.31 per 100,000 for HCH (0.54\u20132.08).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This study provides the first nationwide birth prevalence estimates for ACH and HCH in France, leveraging data from BNDMR. ACH is often identified prenatally, whereas HCH is predominantly diagnosed postnatally. The prevalence of HCH may be underestimated due to under-recognition of milder forms. With the emergence of specific therapies for ACH, and for HCH in the near future, strengthening specialized care pathways is critical to ensure equitable access to timely diagnosis and interventions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Clinical trial number<\/jats:title>\n                    <jats:p>Not applicable.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13023-025-04069-5","type":"journal-article","created":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:39:27Z","timestamp":1762162767000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Achondroplasia and hypochondroplasia in France: a nationwide epidemiological analysis"],"prefix":"10.1186","volume":"20","author":[{"given":"Genevieve","family":"Baujat","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc-Antoine","family":"Hamandjian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne-Sophie","family":"Jannot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Karam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Val\u00e9rie","family":"Cormier-Daire","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,11,3]]},"reference":[{"issue":"9582","key":"4069_CR1","doi-asserted-by":"publisher","first-page":"162","DOI":"10.1016\/s0140-6736(07)61090-3","volume":"370","author":"WA Horton","year":"2007","unstructured":"Horton WA, Hall JG, Hecht JT, Achondroplasia. Lancet. 2007;370(9582):162\u201372. https:\/\/doi.org\/10.1016\/s0140-6736(07)61090-3.","journal-title":"Lancet"},{"issue":"1","key":"4069_CR2","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.berh.2007.12.008","volume":"22","author":"G Baujat","year":"2008","unstructured":"Baujat G, Legeai-Mallet L, Finidori G, Cormier-Daire V, Le Merrer M, Achondroplasia. Best Pract Res Clin Rheumatol. 2008;22(1):3\u201318. https:\/\/doi.org\/10.1016\/j.berh.2007.12.008.","journal-title":"Best Pract Res Clin Rheumatol"},{"issue":"10","key":"4069_CR3","doi-asserted-by":"publisher","first-page":"2297","DOI":"10.1002\/ajmg.a.61787","volume":"182","author":"PK Foreman","year":"2020","unstructured":"Foreman PK, van Kessel F, van Hoorn R, van den Bosch J, Shediac R, Landis S. Birth prevalence of achondroplasia: A systematic literature review and meta-analysis. Am J Med Genet A. 2020;182(10):2297\u2013316. https:\/\/doi.org\/10.1002\/ajmg.a.61787.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"4069_CR4","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1186\/s13023-021-01971-6","volume":"16","author":"V Cormier-Daire","year":"2021","unstructured":"Cormier-Daire V, AlSayed M, Ben-Omran T, de Sousa SB, Boero S, Fredwall SO, et al. The first European consensus on principles of management for achondroplasia. Orphanet J Rare Dis. 2021;16(1):333. https:\/\/doi.org\/10.1186\/s13023-021-01971-6.","journal-title":"Orphanet J Rare Dis"},{"issue":"9","key":"4069_CR5","doi-asserted-by":"publisher","first-page":"3639","DOI":"10.1007\/s12325-023-02549-3","volume":"40","author":"MC Murton","year":"2023","unstructured":"Murton MC, Drane ELA, Goff-Leggett DM, Shediac R, O\u2019Hara J, Irving M, et al. Burden and treatment of achondroplasia: A systematic literature review. Adv Ther. 2023;40(9):3639\u201380. https:\/\/doi.org\/10.1007\/s12325-023-02549-3.","journal-title":"Adv Ther"},{"issue":"3","key":"4069_CR6","doi-asserted-by":"publisher","first-page":"711","DOI":"10.1086\/302000","volume":"63","author":"DJ Wilkin","year":"1998","unstructured":"Wilkin DJ, Szabo JK, Cameron R, Henderson S, Bellus GA, Mack ML, et al. Mutations in fibroblast growth-factor receptor 3 in sporadic cases of achondroplasia occur exclusively on the paternally derived chromosome. Am J Hum Genet. 1998;63(3):711\u20136. https:\/\/doi.org\/10.1086\/302000.","journal-title":"Am J Hum Genet"},{"issue":"9","key":"4069_CR7","doi-asserted-by":"publisher","first-page":"1791","DOI":"10.1002\/ajmg.a.61289","volume":"179","author":"A Cold Coi","year":"2019","unstructured":"Coi A, Santoro M, Garne E, Pierini A, Addor MC, Alessandri JL, et al. Epidemiology of achondroplasia: A population-based study in Europe. Am J Med Genet A. 2019;179(9):1791\u20138. https:\/\/doi.org\/10.1002\/ajmg.a.61289","journal-title":"Am J Med Genet A"},{"key":"4069_CR8","unstructured":"Bober MB, Bellus GA, Nikkel SM, Tiller GE. Hypochondroplasia. GeneReviews\u00ae [Internet]. Seattle (WA): University of Washington, Seattle; 2020. https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK1477\/"},{"issue":"6","key":"4069_CR9","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.1016\/j.fertnstert.2022.10.017","volume":"118","author":"KA Wood","year":"2022","unstructured":"Wood KA, Goriely A. The impact of paternal age on new mutations and disease in the next generation. Fertil Steril. 2022;118(6):1001\u201312. https:\/\/doi.org\/10.1016\/j.fertnstert.2022.10.017.","journal-title":"Fertil Steril"},{"issue":"1","key":"4069_CR10","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1002\/ajmg.a.61912","volume":"185","author":"AH Sabir","year":"2021","unstructured":"Sabir AH, Sheikh J, Singh A, Morley E, Cocca A, Cheung MS, et al. Earlier detection of hypochondroplasia: A large single-center UK case series and systematic review. Am J Med Genet A. 2021;185(1):73\u201382. https:\/\/doi.org\/10.1002\/ajmg.a.61912.","journal-title":"Am J Med Genet A"},{"issue":"1","key":"4069_CR11","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1186\/s13023-023-02725-2","volume":"18","author":"T Pichon","year":"2023","unstructured":"Pichon T, Messiaen C, Soussand L, Angin C, Sandrin A, Elarouci N, et al. Overview of patients\u2019 cohorts in the French National rare disease registry. Orphanet J Rare Dis. 2023;18(1):176. https:\/\/doi.org\/10.1186\/s13023-023-02725-2.","journal-title":"Orphanet J Rare Dis"},{"issue":"2","key":"4069_CR12","doi-asserted-by":"publisher","first-page":"102891","DOI":"10.1016\/j.jogoh.2024.102891","volume":"54","author":"AL Vallin","year":"2025","unstructured":"Vallin AL, Gr\u00e9vent D, Bessi\u00e8res B, Salomon LJ, Legeai-Mallet L, Cormier-Daire V, et al. Foetal achondroplasia: prenatal diagnosis, outcome and perspectives. J Gynecol Obstet Hum Reprod. 2025;54(2):102891. https:\/\/doi.org\/10.1016\/j.jogoh.2024.102891.","journal-title":"J Gynecol Obstet Hum Reprod"},{"issue":"3","key":"4069_CR13","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1093\/jamia\/ocab237","volume":"29","author":"AS Jannot","year":"2022","unstructured":"Jannot AS, Messiaen C, Khatim A, Pichon T, Sandrin A. The ongoing French BaMaRa-BNDMR cohort: implementation and deployment of a nationwide information system on rare disease. J Am Med Inf Assoc. 2022;29(3):553\u20138. https:\/\/doi.org\/10.1093\/jamia\/ocab237.","journal-title":"J Am Med Inf Assoc"},{"issue":"1","key":"4069_CR14","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1186\/s13023-022-02442-2","volume":"17","author":"V Cormier-Daire","year":"2022","unstructured":"Cormier-Daire V, AlSayed M, Alves I, Bengoa J, Ben-Omran T, Boero S, et al. Optimising the diagnosis and referral of achondroplasia in europe: European achondroplasia forum best practice recommendations. Orphanet J Rare Dis. 2022;17(1):293. https:\/\/doi.org\/10.1186\/s13023-022-02442-2.","journal-title":"Orphanet J Rare Dis"},{"issue":"3","key":"4069_CR15","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/s41574-021-00595-x","volume":"18","author":"R Savarirayan","year":"2022","unstructured":"Savarirayan R, Ireland P, Irving M, Thompson D, Alves I, Baratela WAR, et al. International consensus statement on the diagnosis, multidisciplinary management and lifelong care of individuals with achondroplasia. Nat Rev Endocrinol. 2022;18(3):173\u201389. https:\/\/doi.org\/10.1038\/s41574-021-00595-x.","journal-title":"Nat Rev Endocrinol"},{"issue":"5","key":"4069_CR16","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1038\/s41574-024-01074-9","volume":"21","author":"R Savarirayan","year":"2025","unstructured":"Savarirayan R, Hoover-Fong J, Ozono K, Backeljauw P, Cormier-Daire V, DeAndrade K, et al. International consensus guidelines on the implementation and monitoring of vosoritide therapy in individuals with achondroplasia. Nat Rev Endocrinol. 2025;21(5):314\u201324. https:\/\/doi.org\/10.1038\/s41574-024-01074-9.","journal-title":"Nat Rev Endocrinol"},{"key":"4069_CR17","unstructured":"Protocole National de Diagnostic et de Soins (PNDS). Achondroplasie: Texte du PNDS. 2025. https:\/\/www.has-sante.fr\/upload\/docs\/application\/pdf\/2025-04\/pnds_ach_04-04-2025_vff.pdf"}],"container-title":["Orphanet Journal of Rare Diseases"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04069-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s13023-025-04069-5\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s13023-025-04069-5.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T09:39:27Z","timestamp":1762162767000},"score":1,"resource":{"primary":{"URL":"https:\/\/ojrd.biomedcentral.com\/articles\/10.1186\/s13023-025-04069-5"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,3]]},"references-count":17,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["4069"],"URL":"https:\/\/doi.org\/10.1186\/s13023-025-04069-5","relation":{},"ISSN":["1750-1172"],"issn-type":[{"value":"1750-1172","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,3]]},"assertion":[{"value":"23 June 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 September 2025","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"3 November 2025","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This non-interventional study was approved by the BNDMR scientific committee (BPD-2018-DIAG-008\/-002) and registered with the French Data Protection Authority (CNIL: MR004) and the AP-HP local registry (#20230314171333). In accordance with French law, patients were informed about the inclusion of their data in BNDMR and had the opportunity to object to its use for research. Only those who did not object were included in our study.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All authors agree with the content of the manuscript. All authors have agreed to the submission and publication of this manuscript.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"GB declares competing interests for advisory consultancy and expert report production for BioMarin, Inozyme, Ipsen, Sanofi, and Alexion; participation in scientific work for Incyte, Ipsen, QED, Ascendis, BioMarin, Alexion, Clementia, and Therachon Pfizer; and writing articles and interventions for Elsevier, BioMarin, Ipsen, and Alexion. MAH is a BioMarin employee and has stock options. ASJ and PK have no conflicts of interest to declare. VCD declares competing interests related to advisory consultancy or interventions for BioMarin and QED.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"555"}}