{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:21:59Z","timestamp":1791400919407,"version":"4.3.3"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T00:00:00Z","timestamp":1772064000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Legg\u2013Calv\u00e9\u2013Perthes disease (LCPD) is a rare disease caused by avascular necrosis of the femoral head. Although its etiology is still not fully understood, evidence suggests that heritable prothrombotic and inflammatory factors, as well as environmental factors, may be implicated in its onset and progress. The objective of this study is to describe the genetic, biochemical, and environmental factors that may be associated with the etiology of LCPD. This study was conducted in three families and included seven related patients with an LCPD diagnosis. We evaluated the following gene alterations using real-time PCR: MTHFR, CBS, COL1A1, COL2A1, PT, FVL, FVIII, FIX, PAI-1, eNOS, IL-23R, TNF-\u03b1, RANNK, RANNK-L, OPG and IL-6. Additionally, we assessed fourteen thrombophilia-associated biochemical markers, as well as environmental factors that may be associated with the etiology of LCPD in family cases. The results show different hemostatic alterations in every individual analyzed, presenting out-of-range values in one or more parameters. Concentrations of hemoglobin and fibrinogen and the FIX activity percentage showed statistically significant differences (p &lt; 0.001) when compared with healthy controls. All patients presented at least one mutated allele for the MTFHR (rs1801133), IL-23R (rs1569922) and OPG (rs2073618) polymorphisms, as well as isolated cases with other genetic variants. Our results show environmental elements from every family, and hemostatic and inflammatory disorders, may be involved in the development of LCPD. Furthermore, genetic variants could contribute to the onset of the disease. This study highlights the multifactorial nature of this pathology, involving various environmental, genetic, inflammatory, and prothrombotic factors in three families that included seven patients diagnosed with LCPD.<\/jats:p>","DOI":"10.3390\/ijms27052195","type":"journal-article","created":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T10:33:02Z","timestamp":1772101982000},"page":"2195","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Familial Cases of Legg\u2013Calv\u00e9\u2013Perthes Disease\u2014Hemostatic and Molecular Markers"],"prefix":"10.3390","volume":"27","author":[{"given":"Edgar","family":"Hern\u00e1ndez-Zamora","sequence":"first","affiliation":[{"name":"Genomic Medicine, Instituto Nacional de Rehabilitaci\u00f3n \u201cLuis Guillermo Ibarra\u201d, Calzada M\u00e9xico-Xochimilco 289, Arenal de Guadalupe, Tlalpan 14389, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4447-8343","authenticated-orcid":false,"given":"Armando Odiseo","family":"Rodr\u00edguez-Olivas","sequence":"additional","affiliation":[{"name":"Instituto de Ciencias Biom\u00e9dicas, Universidad Aut\u00f3noma de Ciudad Ju\u00e1rez, Campus Cuauht\u00e9moc, Km. 3.5 Carretera An\u00e1huac s\/n, An\u00e1huac, Municipio de Cuauht\u00e9moc 31600, Chihuahua, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3411-6231","authenticated-orcid":false,"given":"Marlene Alejandra","family":"Galicia-Alvarado","sequence":"additional","affiliation":[{"name":"Neurociencias Cl\u00ednicas, Instituto Nacional de Rehabilitaci\u00f3n \u201cLuis Guillermo Ibarra\u201d, Calzada M\u00e9xico-Xochimilco 289, Arenal de Guadalupe, Tlalpan 14389, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonora","family":"Casas-\u00c1vila","sequence":"additional","affiliation":[{"name":"Genomic Medicine, Instituto Nacional de Rehabilitaci\u00f3n \u201cLuis Guillermo Ibarra\u201d, Calzada M\u00e9xico-Xochimilco 289, Arenal de Guadalupe, Tlalpan 14389, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika","family":"Rosales-Cruz","sequence":"additional","affiliation":[{"name":"Morphology Department, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Prolongaci\u00f3n de Carpio y Plan de Ayala s\/n, Col. Santo Tom\u00e1s, Gustavo A. Madero 11340, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cesar","family":"Zavala-Hern\u00e1ndez","sequence":"additional","affiliation":[{"name":"Clinical Pathology Laboratory, Instituto Nacional de Rehabilitaci\u00f3n \u201cLuis Guillermo Ibarra\u201d, Calzada M\u00e9xico-Xochimilco 289, Arenal de Guadalupe, Tlalpan 14389, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4951-6484","authenticated-orcid":false,"given":"Elba","family":"Reyes-Maldonado","sequence":"additional","affiliation":[{"name":"Morphology Department, Escuela Nacional de Ciencias Biol\u00f3gicas, Instituto Polit\u00e9cnico Nacional, Prolongaci\u00f3n de Carpio y Plan de Ayala s\/n, Col. Santo Tom\u00e1s, Gustavo A. Madero 11340, Mexico City, Mexico"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1186\/s13023-022-02275-z","article-title":"Legg-Calv\u00e9-Perthes disease overview","volume":"17","year":"2022","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"659","DOI":"10.2106\/JBJS.J.01834","article-title":"Pathophysiology and new strategies for the treatment of Legg-Calv\u00e9-Perthes disease","volume":"94","author":"Kim","year":"2012","journal-title":"J. Bone Jt. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S152","DOI":"10.1097\/BPO.0b013e318223b423","article-title":"Natural history of early-onset and late-onset Legg-Calve-Perthes disease","volume":"31","author":"Joseph","year":"2011","journal-title":"J. Pediatr. 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