Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects
Abstract
:1. Introduction
2. Etiopathogenesis
3. Epidemiology
4. Genetic Aspects
5. Epigenetics
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Kotlarsky, P.; Haber, R.; Bialik, V.; Eidelman, M. Developmental dysplasia of the hip: What has changed in the last 20 years? World J. Orthop. 2015, 6, 886–901. [Google Scholar] [CrossRef]
- Guille, J.T.; Pizzutillo, P.D.; MacEwen, G.D. Development dysplasia of the hip from birth to six months. J. Am. Acad. Orthop. Surg. 2000, 8, 232–242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- American Academy of Pediatrics. Clinical practice guideline: Early detection of developmental dysplasia of the hip. Committee on Quality Improvement, Subcommittee on Developmental Dysplasia of the Hip. Pediatrics 2000, 105, 896–905. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Trizno, A.A.; Jones, A.S.; Carry, P.M.; Georgopoulos, G. The Prevalence and Treatment of Hip Dysplasia in Prader-Willi Syndrome (PWS). J. Pediatr. Orthop. 2018, 38, e151–e156. [Google Scholar] [CrossRef] [PubMed]
- Vargas Lebrón, C.; Ruiz Montesino, M.D.; Moreira Navarrete, V.; Aróstegui Gorospe, J.I. Síndrome tricorinofalángico. Reumatol. Clín. 2018, in press. [Google Scholar] [CrossRef] [PubMed]
- Langereis, E.J.; den Os, M.M.; Breen, C.; Jones, S.A.; Knaven, O.C.; Mercer, J.; Miller, W.P.; Kelly, P.M.; Kennedy, J.; Ketterl, T.G.; et al. Progression of Hip Dysplasia in Mucopolysaccharidosis Type I Hurler After Successful Hematopoietic Stem Cell Transplantation. J. Bone Joint Surg. Am. 2016, 98, 386–395. [Google Scholar] [CrossRef] [Green Version]
- Sankar, W.N. Complete redirectional acetabular osteotomies for neurogenic and syndromic hip dysplasia. J. Pediatr. Orthop. 2013, 33 (Suppl. S1), S39–S44. [Google Scholar] [CrossRef]
- Auth, P.C.; Kerstein, M.D. Physician Assistant Review; Lippincott Williams & Wilkins: Philadelphia, PA, USA, 2012; ISBN 978-1-4511-7129-7. [Google Scholar]
- Schwend, R.M.; Shaw, B.A.; Segal, L.S. Evaluation and treatment of developmental hip dysplasia in the newborn and infant. Pediatr. Clin. N. Am. 2014, 61, 1095–1107. [Google Scholar] [CrossRef]
- Thomas, S.R.Y.W. A review of long-term outcomes for late presenting developmental hip dysplasia. Bone Joint J. 2015, 97, 729–733. [Google Scholar] [CrossRef]
- Wang, T.-M.; Wu, K.-W.; Shih, S.-F.; Huang, S.-C.; Kuo, K.N. Outcomes of open reduction for developmental dysplasia of the hip: Does bilateral dysplasia have a poorer outcome? J. Bone Joint Surg. Am. 2013, 95, 1081–1086. [Google Scholar] [CrossRef]
- Zídka, M.; Džupa, V. National Register of Joint Replacement Reflecting the Treatment of Developmental Dysplasia of the Hip in Newborns. Acta Chir. Orthop. Traumatol. Cech. 2019, 86, 324–329. [Google Scholar] [PubMed]
- Bache, C.E.; Clegg, J.; Herron, M. Risk factors for developmental dysplasia of the hip: Ultrasonographic findings in the neonatal period. J. Pediatr. Orthop. B 2002, 11, 212–218. [Google Scholar] [PubMed]
- Broadhurst, C.; Rhodes, A.M.L.; Harper, P.; Perry, D.C.; Clarke, N.M.P.; Aarvold, A. What is the incidence of late detection of developmental dysplasia of the hip in England? A 26-year national study of children diagnosed after the age of one. Bone Joint J. 2019, 101, 281–287. [Google Scholar] [CrossRef] [PubMed]
- Marks, D.S.; Clegg, J.; Al-Chalabi, A.N. Routine ultrasound screening for neonatal hip instability. Can it abolish late-presenting congenital dislocation of the hip? J. Bone Joint Surg. Br. 1994, 76, 534–538. [Google Scholar] [CrossRef] [PubMed]
- Furnes, O.; Lie, S.A.; Espehaug, B.; Vollset, S.E.; Engesaeter, L.B.; Havelin, L.I. Hip disease and the prognosis of total hip replacements: A review of 53 698 primary total hip replacements reported to the norwegian arthroplasty register 1987–99. J. Bone Joint Surg. Br. Vol. 2001, 83, 579. [Google Scholar] [CrossRef]
- Weinstein, S.L.; Mubarak, S.J.; Wenger, D.R. Developmental hip dysplasia and dislocation: Part II. Instr. Course Lect. 2004, 53, 531–542. [Google Scholar] [CrossRef]
- Woodacre, T.; Ball, T.; Cox, P. Epidemiology of developmental dysplasia of the hip within the UK: Refining the risk factors. J. Child. Orthop. 2016, 10, 633–642. [Google Scholar] [CrossRef] [Green Version]
- Pollet, V.; Percy, V.; Prior, H.J. Relative Risk and Incidence for Developmental Dysplasia of the Hip. J. Pediatr. 2017, 181, 202–207. [Google Scholar] [CrossRef]
- Loder, R.T.; Shafer, C. The demographics of developmental hip dysplasia in the Midwestern United States (Indiana). J. Child. Orthop. 2015, 9, 93–98. [Google Scholar] [CrossRef] [Green Version]
- Wenger, D.; Düppe, H.; Nilsson, J.-Å.; Tiderius, C.J. Incidence of Late-Diagnosed Hip Dislocation After Universal Clinical Screening in Sweden. JAMA Netw. Open 2019, 2, e1914779. [Google Scholar] [CrossRef] [Green Version]
- Ömeroğlu, H.; Akceylan, A.; Köse, N. Associations between risk factors and developmental dysplasia of the hip and ultrasonographic hip type: A retrospective case control study. J. Child. Orthop. 2019, 13, 161–166. [Google Scholar] [CrossRef] [PubMed]
- Gyurkovits, Z.; Sohár, G.; Baricsa, A.; Németh, G.; Orvos, H.; Dubs, B. Early detection of developmental dysplasia of hip by ultrasound. HIP Int. 2019. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Aronsson, D.D.; Goldberg, M.J.; Kling, T.F.; Roy, D.R. Developmental dysplasia of the hip. Pediatrics 1994, 94, 201–208. [Google Scholar] [PubMed]
- Stein-Zamir, C.; Volovik, I.; Rishpon, S.; Sabi, R. Developmental dysplasia of the hip: Risk markers, clinical screening and outcome. Pediatr. Int. 2008, 50, 341–345. [Google Scholar] [CrossRef] [PubMed]
- De Goiano, E.O.; Akkari, M.; Pupin, J.P.; Santili, C. The epidemiology of developmental dysplasia of the hip in males. Acta Ortop. Bras. 2020, 28, 26–30. [Google Scholar] [CrossRef]
- Lambeek, A.F.; De Hundt, M.; Vlemmix, F.; Akerboom, B.M.C.; Bais, J.M.J.; Papatsonis, D.N.M.; Mol, B.W.J.; Kok, M. Risk of developmental dysplasia of the hip in breech presentation: The effect of successful external cephalic version. BJOG An Int. J. Obstet. Gynaecol. 2013, 120, 607–612. [Google Scholar] [CrossRef]
- Sarkissian, E.J.; Sankar, W.N.; Baldwin, K.; Flynn, J.M. Is there a predilection for breech infants to demonstrate spontaneous stabilization of DDH instability? J. Pediatr. Orthop. 2014, 34, 509–513. [Google Scholar] [CrossRef]
- Panagiotopoulou, N.; Bitar, K.; Hart, W.J. The association between mode of delivery and developmental dysplasia of the hip in breech infants: A systematic review of 9 cohort studies. Acta Orthop. Belg. 2012, 78, 697–702. [Google Scholar]
- Verbruggen, S.W.; Kainz, B.; Shelmerdine, S.C.; Arthurs, O.J.; Hajnal, J.V.; Rutherford, M.A.; Phillips, A.T.M.; Nowlan, N.C. Altered biomechanical stimulation of the developing hip joint in presence of hip dysplasia risk factors. J. Biomech. 2018, 78, 1. [Google Scholar] [CrossRef]
- Yamamuro, T.; Ishida, K. Recent advances in the prevention, early diagnosis, and treatment of congenital dislocation of the hip in Japan. Clin. Orthop. Relat. Res. 1984, 184, 34–40. [Google Scholar] [CrossRef]
- Rabin, D.L.; Barnett, C.R.; Arnold, W.D.; Freiberger, R.H.; Brooks, G. Untreated congenital hip disease: A study of the epidemiology, natural history, and social aspects of the disease in a navajo population. Am. J. Public Health Nations Health 1965, 55, i3-44. [Google Scholar] [CrossRef] [Green Version]
- Stevenson, D.A.; Mineau, G.; Kerber, R.A.; Viskochil, D.H.; Schaefer, C.; Roach, J.W. Familial Predisposition to Developmental Dysplasia of the Hip. J. Pediatr. Orthop. 2009, 29, 463–466. [Google Scholar] [CrossRef] [PubMed]
- Ortiz-Neira, C.L.; Paolucci, E.O.; Donnon, T. A meta-analysis of common risk factors associated with the diagnosis of developmental dysplasia of the hip in newborns. Eur. J. Radiol. 2012, 81, e344–e351. [Google Scholar] [CrossRef] [PubMed]
- Van Gijzen, A.F.M.; Rouers, E.D.M.; van Douveren, F.Q.M.P.; Dieleman, J.; Hendriks, J.G.E.; Halbertsma, F.J.J.; Bok, L.A. Developmental dysplasia of the hip in children with Down syndrome: Comparison of clinical and radiological examinations in a local cohort. Eur. J. Pediatr. 2019, 178, 559–564. [Google Scholar] [CrossRef]
- Perry, D.C.; Tawfiq, S.M.; Roche, A.; Shariff, R.; Garg, N.K.; James, L.A.; Sampath, J.; Bruce, C.E. The association between clubfoot and developmental dysplasia of the hip. J. Bone Joint Surg. Br. 2010, 92, 1586–1588. [Google Scholar] [CrossRef] [Green Version]
- Jang, S.-A.; Cho, Y.-H.; Byun, Y.-S.; Jeong, D.-G.; Han, I.-H.; Kim, M.-G. Unusual Cause of Hip Pain: Intrusion of the Acetabular Labrum. Hip Pelvis 2015, 27, 49–52. [Google Scholar] [CrossRef] [Green Version]
- Moličnik, A.; Janša, J.; Kocjančič, B.; Kralj-Iglič, V.; Dolinar, D. Secondary hip dysplasia increases risk for early coxarthritis after Legg-Calve-Perthes disease. A study of 255 hips. Comput. Methods Biomech. Biomed. Eng. 2019, 22, 1107–1115. [Google Scholar] [CrossRef]
- Zhao, D.; Hu, W.; Zhao, B.; Zhao, X.; Li, Y.; Zhang, J.; Chen, H.; Wu, Z. Arthroscopic treatment of irreducible hip posterior dislocation caused by acetabular labrum bony Bankart lesions. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi 2019, 33, 676–680. [Google Scholar]
- Lee, S.H.; Jang, W.Y.; Choi, G.W.; Lee, Y.K.; Jung, H.W. Is the Transverse Acetabular Ligament Hypertrophied and Hindering Reduction in Developmental Dysplasia of Hip? Arthroscopy 2018, 34, 1219–1226. [Google Scholar] [CrossRef]
- Zhao, L.; Ma, Q.; Feng, X.; Fan, L.; Jiao, Q.; Wang, S.; Ying, H.; Yang, X. Screening for Developmental Dysplasia of the Hip in Infants in Tibet Identifies Increased Prevalence Associated with Altitude. Med. Sci. Monit. 2019, 25, 5771–5775. [Google Scholar] [CrossRef]
- Feldman, G.J.; Parvizi, J.; Levenstien, M.; Scott, K.; Erickson, J.A.; Fortina, P.; Devoto, M.; Peters, C.L. Developmental Dysplasia of the Hip: Linkage Mapping and Whole Exome Sequencing Identify a Shared Variant in CX 3 CR 1 in All Affected Members of a Large Multigeneration Family. J. Bone Miner. Res. 2013, 28, 2540–2549. [Google Scholar] [CrossRef] [PubMed]
- Feldman, G.; Dalsey, C.; Fertala, K.; Azimi, D.; Fortina, P.; Devoto, M.; Pacifici, M.; Parvizi, J. 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. Clin. Orthop. Relat. Res. 2010, 468, 337–344. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wynne-Davies, R. Acetabular dysplasia and familial joint laxity: Two etiological factors in congenital dislocation of the hip. A review of 589 patients and their families. J. Bone Joint Surg. Br. 1970, 52, 704–716. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhu, L.; Su, G.; Dai, J.; Zhang, W.; Yin, C.; Zhang, F.; Zhu, Z.; Guo, Z.; Fang, J.; Zou, C.; et al. Whole genome sequencing of pairwise human subjects reveals DNA mutations specific to developmental dysplasia of the hip. Genomics 2019, 111, 320–326. [Google Scholar] [CrossRef] [PubMed]
- Feldman, G.; Kappes, D.; Mookerjee-Basu, J.; Freeman, T.; Fertala, A.; Parvizi, J. Novel mutation in Teneurin 3 found to co-segregate in all affecteds in a multi-generation family with developmental dysplasia of the hip. J. Orthop. Res. 2019, 37, 171–180. [Google Scholar] [CrossRef] [Green Version]
- Shi, D.; Dai, J.; Zhu, P.; Qin, J.; Zhu, L.; Zhu, H.; Zhao, B.; Qiu, X.; Xu, Z.; Chen, D.; et al. Association of the D repeat polymorphism in the ASPN gene with developmental dysplasia of the hip: A case-control study in Han Chinese. Arthritis Res. Ther. 2011, 13, R27. [Google Scholar] [CrossRef] [Green Version]
- Zhang, J.; Yan, M.; Zhang, Y.; Yang, H.; Sun, Y. Association analysis on polymorphisms in WISP3 gene and developmental dysplasia of the hip in Han Chinese population: A case-control study. Gene 2018, 664, 192–195. [Google Scholar] [CrossRef]
- Hatzikotoulas, K.; Roposch, A.; Shah, K.M.; Clark, M.J.; Bratherton, S.; Limbani, V.; Steinberg, J.; Zengini, E.; Warsame, K.; Ratnayake, M.; et al. Genome-wide association study of developmental dysplasia of the hip identifies an association with GDF5. Commun. Biol. 2018, 1, 56. [Google Scholar] [CrossRef]
- Duncan, L.E.; Ostacher, M.; Ballon, J. How genome-wide association studies (GWAS) made traditional candidate gene studies obsolete. Neuropsychopharmacology 2019, 44, 1518–1523. [Google Scholar] [CrossRef]
- Feldman, G.J.; Peters, C.L.; Erickson, J.A.; Hozack, B.A.; Jaraha, R.; Parvizi, J. Variable Expression and Incomplete Penetrance of Developmental Dysplasia of the Hip. J. Arthroplast. 2012, 27, 527–532. [Google Scholar] [CrossRef]
- Kolundžić, R.; Trkulja, V.; Mikolaučić, M.; Jovanić Kolundžić, M.; Pavelić, S.K.; Pavelić, K. Association of interleukin-6 and transforming growth factor-β1 gene polymorphisms with developmental hip dysplasia and severe adult hip osteoarthritis: A preliminary study. Cytokine 2011, 54, 125–128. [Google Scholar] [CrossRef] [PubMed]
- Jia, J.; Li, L.; Zhao, Q.; Zhang, L.; Ru, J.; Liu, X.; Li, Q.; Shi, L. Association of a single nucleotide polymorphism in pregnancy-associated plasma protein-A2 with developmental dysplasia of the hip: A case–control study. Osteoarthr. Cartil. 2012, 20, 60–63. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhao, L.; Tian, W.; Pan, H.; Zhu, X.; Wang, J.; Cheng, Z.; Cheng, L.; Ma, X.; Wang, B. Variations of the COL1A1 Gene Promoter and the Relation to Developmental Dysplasia of the Hip. Genet. Test. Mol. Biomark. 2013, 17, 840–843. [Google Scholar] [CrossRef]
- Basit, S.; Alharby, E.; Albalawi, A.M.; Khoshhal, K.I. Whole genome SNP genotyping in a family segregating developmental dysplasia of the hip detected runs of homozygosity on chromosomes 15q13.3 and 19p13.2: SNP genotyping in a family with DDH. Congenit. Anom. 2018, 58, 56–61. [Google Scholar] [CrossRef]
- Liu, S.; Tian, W.; Wang, J.; Cheng, L.; Jia, J.; Ma, X. Two Single-Nucleotide Polymorphisms in the DKK1 Gene Are Associated with Developmental Dysplasia of the Hip in the Chinese Han Female Population. Genet. Test. Mol. Biomark. 2014, 18, 557–561. [Google Scholar] [CrossRef]
- Evangelou, E.; Chapman, K.; Meulenbelt, I.; Karassa, F.B.; Loughlin, J.; Carr, A.; Doherty, M.; Doherty, S.; Gómez-Reino, J.J.; Gonzalez, A.; et al. Large-scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand. Arthritis Rheum. 2009, 60, 1710–1721. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dai, J.; Shi, D.; Zhu, P.; Qin, J.; Ni, H.; Xu, Y.; Yao, C.; Zhu, L.; Zhu, H.; Zhao, B.; et al. Association of a single nucleotide polymorphism in growth differentiate factor 5 with congenital dysplasia of the hip: A case-control study. Arthritis Res. Ther. 2008, 10, R126. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hao, Z.; Dai, J.; Shi, D.; Xu, Z.; Chen, D.; Zhao, B.; Teng, H.; Jiang, Q. Association of a single nucleotide polymorphism in HOXB9 with developmental dysplasia of the hip: A case-control study. J. Orthop. Res. 2014, 32, 179–182. [Google Scholar] [CrossRef] [PubMed]
- Tian, W.; Zhao, L.; Wang, J.; Suo, P.; Wang, J.; Cheng, L.; Cheng, Z.; Jia, J.; Kan, S.; Wang, B.; et al. Association analysis between HOXD9 genes and the development of developmental dysplasia of the hip in Chinese female Han population. BMC Musculoskelet. Disord. 2012, 13, 59. [Google Scholar] [CrossRef] [Green Version]
- Wang, K.; Shi, D.; Zhu, P.; Dai, J.; Zhu, L.; Zhu, H.; Lv, Y.; Zhao, B.; Jiang, Q. Association of a single nucleotide polymorphism in Tbx4 with developmental dysplasia of the hip: A case-control study. Osteoarthr. Cartil. 2010, 18, 1592–1595. [Google Scholar] [CrossRef] [Green Version]
- Sun, Y.; Wang, C.; Hao, Z.; Dai, J.; Chen, D.; Xu, Z.; Shi, D.; Mao, P.; Teng, H.; Gao, X.; et al. A Common Variant Of Ubiquinol-Cytochrome c Reductase Complex Is Associated with DDH. PLoS ONE 2015, 10, e0120212. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Eftekhari, H.; Hosseini, S.R.; Pourreza Baboli, H.; Mafi Golchin, M.; Heidari, L.; Abedian, Z.; Pourbagher, R.; Amjadi-Moheb, F.; Mousavi Kani, S.N.; Nooreddini, H.; et al. Association of interleukin-6 (rs1800796) but not transforming growth factor beta 1 (rs1800469) with serum calcium levels in osteoporotic patients. Gene 2018, 671, 21–27. [Google Scholar] [CrossRef] [PubMed]
- Fernandes, M.T.P.; Fernandes, K.B.P.; Marquez, A.S.; Cólus, I.M.S.; Souza, M.F.; Santos, J.P.M.; Poli-Frederico, R.C. Association of interleukin-6 gene polymorphism (rs1800796) with severity and functional status of osteoarthritis in elderly individuals. Cytokine 2015, 75, 316–320. [Google Scholar] [CrossRef] [PubMed]
- Kämäräinen, O.-P.; Solovieva, S.; Vehmas, T.; Luoma, K.; Riihimäki, H.; Ala-Kokko, L.; Männikkö, M.; Leino-Arjas, P. Common interleukin-6 promoter variants associate with the more severe forms of distal interphalangeal osteoarthritis. Arthritis Res. Ther. 2008, 10, R21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Silverio-Ruiz, K.G.; Martinez, A.E.T.; Garlet, G.P.; Barbosa, C.F.; Silva, J.S.; Cicarelli, R.M.B.; Valentini, S.R.; Abi-Rached, R.S.G.; Junior, C.R. Opposite effects of bFGF and TGF-β on collagen metabolism by human periodontal ligament fibroblasts. Cytokine 2007, 39, 130–137. [Google Scholar] [CrossRef] [PubMed]
- Roelen, B.A.J.; Dijke, P. ten Controlling mesenchymal stem cell differentiation by TGFβ family members. J. Orthop. Sci. 2003, 8, 740–748. [Google Scholar] [CrossRef]
- Vaughn, S.P.; Broussard, S.; Hall, C.R.; Scott, A.; Blanton, S.H.; Milunsky, J.M.; Hecht, J.T. Confirmation of the Mapping of the Camurati–Englemann Locus to 19q13.2 and Refinement to a 3.2-cM Region. Genomics 2000, 66, 119–121. [Google Scholar] [CrossRef]
- Buxton, P.; Edwards, C.; Archer, C.W.; Francis-West, P. Growth/differentiation factor-5 (GDF-5) and skeletal development. J. Bone Joint Surg. Am. 2001, 83 (Suppl. S1), S23–S30. [Google Scholar] [CrossRef]
- Nishitoh, H.; Ichijo, H.; Kimura, M.; Matsumoto, T.; Makishima, F.; Yamaguchi, A.; Yamashita, H.; Enomoto, S.; Miyazono, K. Identification of Type I and Type II Serine/Threonine Kinase Receptors for Growth/Differentiation Factor-5. J. Biol. Chem. 1996, 271, 21345–21352. [Google Scholar] [CrossRef] [Green Version]
- Harada, M.; Takahara, M.; Zhe, P.; Otsuji, M.; Iuchi, Y.; Takagi, M.; Ogino, T. Developmental failure of the intra-articular ligaments in mice with absence of growth differentiation factor 5. Osteoarthr. Cartil. 2007, 15, 468–474. [Google Scholar] [CrossRef] [Green Version]
- Egli, R.J.; Southam, L.; Wilkins, J.M.; Lorenzen, I.; Pombo-Suarez, M.; Gonzalez, A.; Carr, A.; Chapman, K.; Loughlin, J. Functional analysis of the osteoarthritis susceptibility-associated GDF5 regulatory polymorphism. Arthritis Rheum. 2009, 60, 2055–2064. [Google Scholar] [CrossRef] [PubMed]
- Dai, J.; Ikegawa, S. Recent advances in association studies of osteoarthritis susceptibility genes. J. Hum. Genet. 2010, 55, 77–80. [Google Scholar] [CrossRef] [PubMed]
- Liu, J.; Cai, W.; Zhang, H.; He, C.; Deng, L. Rs143383 in the Growth Differentiation Factor 5 ( GDF5 ) Gene Significantly Associated with Osteoarthritis (OA)-A Comprehensive Meta-analysis. Int. J. Med. Sci. 2013, 10, 312–319. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rouault, K.; Scotet, V.; Autret, S.; Gaucher, F.; Dubrana, F.; Tanguy, D.; El Rassi, C.Y.; Fenoll, B.; Férec, C. Evidence of association between GDF5 polymorphisms and congenital dislocation of the hip in a Caucasian population. Osteoarthr. Cartil. 2010, 18, 1144–1149. [Google Scholar] [CrossRef] [Green Version]
- Kiepe, D.; Ciarmatori, S.; Haarmann, A.; Tönshoff, B. Differential expression of IGF system components in proliferating vs. differentiating growth plate chondrocytes: The functional role of IGFBP-5. Am. J. Physiol. Endocrinol. Metab. 2006, 290, E363–E371. [Google Scholar] [CrossRef] [Green Version]
- Overgaard, M.T.; Boldt, H.B.; Laursen, L.S.; Sottrup-Jensen, L.; Conover, C.A.; Oxvig, C. Pregnancy-associated Plasma Protein-A2 (PAPP-A2), a Novel Insulin-like Growth Factor-binding Protein-5 Proteinase. J. Biol. Chem. 2001, 276, 21849–21853. [Google Scholar] [CrossRef] [Green Version]
- Yan, X.; Baxter, R.C.; Firth, S.M. Involvement of Pregnancy-Associated Plasma Protein-A2 in Insulin-Like Growth Factor (IGF) Binding Protein-5 Proteolysis during Pregnancy: A Potential Mechanism for Increasing IGF Bioavailability. J. Clin. Endocrinol. Metab. 2010, 95, 1412–1420. [Google Scholar] [CrossRef]
- Chen, Y.; Li, L.; Wang, E.; Zhang, L.; Zhao, Q. Abnormal expression of Pappa2 gene may indirectly affect mouse hip development through the IGF signaling pathway. Endocrine 2019, 65, 440–450. [Google Scholar] [CrossRef]
- Allis, C.D.; Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 2016, 17, 487–500. [Google Scholar] [CrossRef]
- Jones, B. Dissecting the roles of Pol V. Nat. Rev. Genet. 2012, 13, 673. [Google Scholar] [CrossRef]
- Greer, J.; McCombe, P.A. The role of epigenetic mechanisms and processes in autoimmune disorders. Biol. Targets Ther. 2012, 6, 307. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baghdadi, T.; Nejadhosseinian, M.; Shirkoohi, R.; Mostafavi Tabatabaee, R.; Tamehri, S.S.; Saffari, M.; Mortazavi, S.M.J. DNA hypermethylation of GDF5 in developmental dysplasia of the hip (DDH). Mol. Genet. Genom. Med. 2019, 7, e887. [Google Scholar]
- Da Silva, M.A.; Yamada, N.; Clarke, N.M.P.; Roach, H.I. Cellular and epigenetic features of a young healthy and a young osteoarthritic cartilage compared with aged control and OA cartilage. J. Orthop. Res. 2009, 27, 593–601. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ning, B.; Jin, R.; Wang, D.; Sun, J. The H19/let-7 feedback loop contributes to developmental dysplasia and dislocation of the hip. Physiol. Res. 2019, 275–284. [Google Scholar] [CrossRef]
- Kim, K.-I.; Park, Y.-S.; Im, G.-I. Changes in the epigenetic status of the SOX-9 promoter in human osteoarthritic cartilage. J. Bone Miner. Res. 2013, 28, 1050–1060. [Google Scholar] [CrossRef]
- Martinez-Sanchez, A.; Dudek, K.A.; Murphy, C.L. Regulation of human chondrocyte function through direct inhibition of cartilage master regulator SOX9 by microRNA-145 (miRNA-145). J. Biol. Chem. 2012, 287, 916–924. [Google Scholar] [CrossRef] [Green Version]
Risk Factor | Reported Associations |
---|---|
Female gender | In literature female gender shows seven to nine times more frequent DDH diagnosis at birth, than male newborns [19,23]. |
Left hip joint | Isolated right hip dysplasia is the least common type. The most common is the affection of the left hip due to fetal positions where the left hip is leaning towards the spine of the mother [24], bilateral affection is also common [25,26]. |
Gravidity | Post-terminal gravidity increases the chance of DDH [19]. |
Delivery | There is a significant risk of DDH due to the high strain on lower extremities posed by the breech presentation [27], although breech babies are more likely to experience spontaneous resolution [22,28]. Vaginal delivery, although having other benefits, compared to cesarean section significantly increases the statistical risk for DDH [29]. |
Limited fetal mobility | Factors such as oligohydramnios [30], high birth weight (HBW) or primiparity [18], present an increased risk for DDH. |
Swaddling | Certain populations have reported higher incidence rates of DDH due to tight swaddling techniques [31,32]. |
Family history | Family history and its genetic contribution increase twelvefold the risk of DDH incidence in first-degree relatives [33,34]. Caucasian population: IL-6, TGFB1 Asian population: COL2A1, DKK1, HOXB9, HOXD9, WISP3 Non-specific: COL1A1, CX3CR1, GDF-5, PAPPA2 |
Presence of different malformations | Down’s syndrome or foot malformations e.g. clubfoot [35,36]. Torticollis, metatarsus adductus, laxity of tendons. |
Intra- or extra-articular instability of the joint | Usually consequences of poor care and/or injuries causing damage to the hip joint, e.g. inflammation of surrounding tendons, some diseases (Legg–Calvé–Perthes Disease), acetabular labrum lesions or abnormalities [37,38,39]. Ligamentous laxity leading to instability. In a recent study, hypertrophy of the Transverse Acetabular Ligament did not prove to be causative in DDH [40]. |
Altitude | A recent study in Tibet found increased DDH incidence with increasing altitude [41]. |
Gene | Localization | Reference SNP | Study Design | Original Publication |
---|---|---|---|---|
ASPN | 9q22.31 | D repeat polymorphism | CGAS | Shi, D. et al., 2011 [47] |
BMS1 | 10q11.21 | rs201298233 | WES | Zhu, L. et al., 2019 [45] |
COL1A1 | 17q21.33 | rs113647555 | CGAS | Zhao, L et al., 2013 [54] |
CX3CR1 | 3q22.2 | rs3732378 | GWLA | Feldman, G.J. et al., 2013 [42] |
rs3732379 | GWLA | Basit, S. et al., 2018 [55] | ||
DKK1 | 10q21.1 | rs1569198 | CGAS | Liu, S. et al., 2014 [56] |
FRZB | 2q32.1 | rs288326 | GWAS | Evangelou E. et al., 2009 [57] |
GDF5 | 20q11.22 | rs143383 | CGAS | Dai, J. et al., 2008 [58] |
rs143384 | GWAS | Hatzikotoulas, K. et al., 2018 [49] | ||
HOXB9 | 17q21.32 | rs2303486, rs8844 | CGAS | Hao, Z. et al., 2014 [59] |
HOXD9 | 2q31.1 | rs711819 | CGAS | Tian, W. et al., 2012 [60] |
IL-6 | 7p15.3 | rs1800796 | RFLP | Kolundžić, R. et al., 2011 [52] |
PAPPA2 | 1q25.2 | rs726252 | CGAS | Jia, J. et al., 2012 [53] |
TBX4 | 17q23.2 | rss3744448 | CGAS | Wang, K. et al., 2010 [61] |
TENM3 | 4q34.3-q35.1 | rs183721398 | WES | Feldman, G.J. et al., 2019 [46] |
TGFB1 | 19q13.2 | rs1800470 | RFLP | Kolundžić, R. et al., 2011 [52] |
UQCC1 | 20q11.22 | rs6060373 | GWAS | Sun, Y. et al., 2015 [62] |
WISP3 | 6q21 | rs1230345 | CGAS | Zhang, J. et al., 2018 [48] |
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Harsanyi, S.; Zamborsky, R.; Krajciova, L.; Kokavec, M.; Danisovic, L. Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects. Medicina 2020, 56, 153. https://doi.org/10.3390/medicina56040153
Harsanyi S, Zamborsky R, Krajciova L, Kokavec M, Danisovic L. Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects. Medicina. 2020; 56(4):153. https://doi.org/10.3390/medicina56040153
Chicago/Turabian StyleHarsanyi, Stefan, Radoslav Zamborsky, Lubica Krajciova, Milan Kokavec, and Lubos Danisovic. 2020. "Developmental Dysplasia of the Hip: A Review of Etiopathogenesis, Risk Factors, and Genetic Aspects" Medicina 56, no. 4: 153. https://doi.org/10.3390/medicina56040153