{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T12:57:53Z","timestamp":1793105873223,"version":"4.5.0"},"reference-count":26,"publisher":"Bioscientifica","issue":"10","license":[{"start":{"date-parts":[[2026,2,13]],"date-time":"2026-02-13T00:00:00Z","timestamp":1770940800000},"content-version":"vor","delay-in-days":2327,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2019,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Developmental dysplasia of the hip (DDH) is one of the most prevalent congenital malformations. It has a wide spectrum of anatomical abnormalities of the hip joint and is characterized by mild or incomplete formation of the acetabulum leading to laxity of the joint capsule, secondary deformity of the proximal femur and irreducible hip dislocation. It is the leading cause of early hip osteoarthritis in young individuals. Both genetic and environmental factors have been proposed to play an important role in the pathogenesis of DDH. A high prevalence is present in Asian, Caucasian, Mediterranean and American populations, with females being more frequently affected. We evaluated a variety of genetic studies indexed in the PubMed database. Several susceptive genes, including WISP3, PAPPA2, HOXB9, HOXD9, GDF5, TGF Beta 1, CX3CR1, UQCC, COL1A1, TbX4 and ASPN have been identified as being associated with the development of DDH. Moreover, genetic association has also been reported between hip dysplasia and other comorbidities. Even though genetic components are a crucial part in the aetiology of DDH, several DDH susceptibility genes need further investigation. The purpose of this review is to present current literature evidence regarding genes responsible for DDH development.<\/jats:p>\n                  <jats:p>Cite this article: EFORT Open Rev 2019;4:595-601. DOI: 10.1302\/2058-5241.4.190006<\/jats:p>","DOI":"10.1302\/2058-5241.4.190006","type":"journal-article","created":{"date-parts":[[2019,10,1]],"date-time":"2019-10-01T08:02:33Z","timestamp":1569916953000},"page":"595-601","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-16","source":"Crossref","is-referenced-by-count":41,"title":["Developmental dysplasia of the hip: a systematic literature review of the genes related with its occurrence"],"prefix":"10.1530","volume":"4","author":[{"given":"Ioannis","family":"Gkiatas","sequence":"first","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasia","family":"Boptsi","sequence":"additional","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitra","family":"Tserga","sequence":"additional","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioannis","family":"Gelalis","sequence":"additional","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dimitrios","family":"Kosmas","sequence":"additional","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilios","family":"Pakos","sequence":"additional","affiliation":[{"name":"1Orthopaedic Department, School of Medicine, University of Ioannina, Ioannina, Greece"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","published-online":{"date-parts":[[2019,10,1]]},"reference":[{"key":"2026070711233994700_bibr1-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.gene.2018.04.020","article-title":"Association analysis on polymorphisms in WISP3 gene and developmental dysplasia of the hip in Han Chinese population: a case-control study","volume":"664","author":"Zhang","year":"2018","journal-title":"Gene"},{"key":"2026070711233994700_bibr2-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1111\/cga.12235","article-title":"Whole genome SNP genotyping in a family segregating developmental dysplasia of the hip detected runs of homozygosity on chromosomes 15q13.3 and 19p13.2","volume":"58","author":"Basit","year":"2018","journal-title":"Congenit Anom (Kyoto)"},{"key":"2026070711233994700_bibr3-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"793","DOI":"10.1007\/s00264-015-2675-0","article-title":"Association of TGFB1 29C\/T and IL6 -572G\/C polymorphisms with developmental hip dysplasia: a case-control study in adults with severe osteoarthritis","volume":"39","author":"\u010cengi\u0107","year":"2015","journal-title":"Int Orthop"},{"key":"2026070711233994700_bibr4-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1016\/j.arth.2014.05.014","article-title":"Linkage mapping and whole exome sequencing identify a shared variant in CX3CR1 in a large multi-generation family","volume":"29","author":"Feldman","year":"2014","journal-title":"J Arthroplasty"},{"key":"2026070711233994700_bibr5-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1111\/cge.12755","article-title":"Developmental dysplasia of the hip: usefulness of next generation genomic tools for characterizing the underlying genes \u2013 a mini review","volume":"90","author":"Basit","year":"2016","journal-title":"Clin Genet"},{"key":"2026070711233994700_bibr6-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1111\/eci.12084","article-title":"Heritability and sibling recurrent risk of developmental dysplasia of the hip in Chinese population","volume":"43","author":"Li","year":"2013","journal-title":"Eur J Clin Invest"},{"key":"2026070711233994700_bibr7-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1002\/jor.23294","article-title":"CX3CR1 polymorphisms associated with an increased risk of developmental dysplasia of the hip in human","volume":"35","author":"Li","year":"2017","journal-title":"J Orthop Res"},{"key":"2026070711233994700_bibr8-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"e0120212","DOI":"10.1371\/journal.pone.0120212","article-title":"A common variant of ubiquinol-cytochrome c reductase complex is associated with DDH","volume":"10","author":"Sun","year":"2015","journal-title":"PLoS One"},{"key":"2026070711233994700_bibr9-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"12239","DOI":"10.1074\/jbc.M413284200","article-title":"Interleukin-6 regulation of transforming growth factor (TGF)-\u03b2 receptor compartmentalization and turnover enhances TGF-\u03b21 signaling","volume":"280","author":"Zhang","year":"2005","journal-title":"J Biol Chem"},{"key":"2026070711233994700_bibr10-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"1063","DOI":"10.1007\/s11427-013-4514-0","article-title":"Two single nucleotide polymorphisms in the GDF5 gene are associated with development dysplasia of the hip in Chinese female population","volume":"56","author":"Zhao","year":"2013","journal-title":"Sci China Life Sci"},{"key":"2026070711233994700_bibr11-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"R126","DOI":"10.1186\/ar2540","article-title":"Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: a case-control study","volume":"10","author":"Dai","year":"2008","journal-title":"Arthritis Res Ther"},{"key":"2026070711233994700_bibr12-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1111\/j.1365-2362.2012.02682.x","article-title":"Genetic study on developmental dysplasia of the hip","volume":"42","author":"Shi","year":"2012","journal-title":"Eur J Clin Invest"},{"key":"2026070711233994700_bibr13-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"1144","DOI":"10.1016\/j.joca.2010.05.018","article-title":"Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population","volume":"18","author":"Rouault","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"key":"2026070711233994700_bibr14-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1016\/j.cyto.2011.02.004","article-title":"Association of interleukin-6 and transforming growth factor-\u03b21 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: a preliminary study","volume":"54","author":"Kolund\u017ei\u0107","year":"2011","journal-title":"Cytokine"},{"key":"2026070711233994700_bibr15-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.joca.2011.10.004","article-title":"Association of a single nucleotide polymorphism in pregnancy-associated plasma protein-A2 with developmental dysplasia of the hip: a case-control study","volume":"20","author":"Jia","year":"2012","journal-title":"Osteoarthritis Cartilage"},{"key":"2026070711233994700_bibr16-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"979520","DOI":"10.1155\/2014\/979520","article-title":"A replication study for the association of rs726252 in PAPPA2 with developmental dysplasia of the hip in Chinese Han population","volume":"2014","author":"Shi","year":"2014","journal-title":"BioMed Res Int"},{"key":"2026070711233994700_bibr17-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1186\/1471-2474-13-59","article-title":"Association analysis between HOXD9 genes and the development of developmental dysplasia of the hip in Chinese female Han population","volume":"13","author":"Tian","year":"2012","journal-title":"BMC Musculoskelet Disord"},{"key":"2026070711233994700_bibr18-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1002\/jor.22507","article-title":"Association of a single nucleotide polymorphism in HOXB9 with developmental dysplasia of the hip: a case-control study","volume":"32","author":"Hao","year":"2014","journal-title":"J Orthop Res"},{"key":"2026070711233994700_bibr19-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"840","DOI":"10.1089\/gtmb.2013.0179","article-title":"Variations of the COL1A1 gene promoter and the relation to developmental dysplasia of the hip","volume":"17","author":"Zhao","year":"2013","journal-title":"Genet Test Mol Biomarkers"},{"key":"2026070711233994700_bibr20-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"1592","DOI":"10.1016\/j.joca.2010.09.008","article-title":"Association of a single nucleotide polymorphism in Tbx4 with developmental dysplasia of the hip: a case-control study","volume":"18","author":"Wang","year":"2010","journal-title":"Osteoarthritis Cartilage"},{"key":"2026070711233994700_bibr21-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"R27","DOI":"10.1186\/ar3252","article-title":"Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: a case-control study in Han Chinese","volume":"13","author":"Shi","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"2026070711233994700_bibr22-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1186\/ar3291","article-title":"Knee osteoarthritis, lumbar-disc degeneration and developmental dysplasia of the hip-an emerging genetic overlap","volume":"13","author":"Loughlin","year":"2011","journal-title":"Arthritis Res Ther"},{"key":"2026070711233994700_bibr23-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"102","DOI":"10.1186\/1471-2350-9-102","article-title":"A novel insertion mutation in the cartilage-derived morphogenetic protein-1 (CDMP1) gene underlies Grebe-type chondrodysplasia in a consanguineous Pakistani family","volume":"9","author":"Basit","year":"2008","journal-title":"BMC Med Genet"},{"key":"2026070711233994700_bibr24-2058-5241.4.190006","first-page":"64","article-title":"Same genetic mutation, different genetic disease phenotype","volume":"1","author":"Lobo","year":"2008","journal-title":"Nature Education"},{"key":"2026070711233994700_bibr25-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1097\/BPO.0000000000000644","article-title":"Hip dysplasia in children with osteogenesis imperfecta: association with collagen type I C-propeptide mutations","volume":"37","author":"Kishta","year":"2017","journal-title":"J Pediatr Orthop"},{"key":"2026070711233994700_bibr26-2058-5241.4.190006","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s11999-009-1073-6","article-title":"The Otto Aufranc Award: identification of a 4 Mb region on chromosome 17q21 linked to developmental dysplasia of the hip in one 18-member, multigeneration family","volume":"468","author":"Feldman","year":"2010","journal-title":"Clin Orthop Relat Res"}],"container-title":["EFORT Open Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/online.boneandjoint.org.uk\/doi\/pdf\/10.1302\/2058-5241.4.190006","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/online.boneandjoint.org.uk\/doi\/full-xml\/10.1302\/2058-5241.4.190006","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.bioscientifica.com\/eor\/article-pdf\/4\/10\/595\/16396\/2058-5241.4.190006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.bioscientifica.com\/eor\/article-pdf\/4\/10\/595\/16396\/2058-5241.4.190006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T15:59:40Z","timestamp":1783439980000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.bioscientifica.com\/eor\/article\/4\/10\/595\/2126\/Developmental-dysplasia-of-the-hip-a-systematic"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,1]]},"references-count":26,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2019,10,1]]},"published-print":{"date-parts":[[2019,10,1]]}},"URL":"https:\/\/doi.org\/10.1302\/2058-5241.4.190006","relation":{},"ISSN":["2058-5241"],"issn-type":[{"value":"2058-5241","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,1]]}}}