Hereditary Multiple Exostoses: Current Insights

References

• Wicklund CL, Pauli RM, Johnson DR, Hecht JT. Natural history of hereditary multiple exostoses. Am J Med Genet.1995;55:43–46. doi:10.1002/ajmg.13205501137702095
   PubMed Web of Science ®Google Scholar
• Schmale GA, Conrad EU, Raskind WH. The natural history of hereditary multiple exostoses. J Bone Joint Surg Am.1994;76:986–992. doi:10.2106/00004623-199407000-000058027127
   PubMed Web of Science ®Google Scholar
• Ryckx A, Somers JF, Allaert L. Hereditary multiple exostosis. Acta Orthop Belg. 2013;79(6):597–607.24563962
   PubMed Web of Science ®Google Scholar
• Campanacci M. Bone and Soft Tissue Tumors. Bologna: Springer-Verlag Wien GmbH; 1990.
   Google Scholar
• Solomon L. Hereditary multiple exostosis. J Bone Joint Surg. 1963;45-B:B: 292–304. doi:10.1302/0301-620X.45B2.292
   Web of Science ®Google Scholar
• Matsuno T 1, Ichioka Y, Yagi T, Ishii S. Spindle-cell sarcoma in patients who have osteochondromatosis. A report of two cases. J Bone Joint Surg Am. 1988;70(1):137–141. doi:10.2106/00004623-198870010-000252826487
   PubMed Web of Science ®Google Scholar
• Krooth RS, Maklin MT, Hilsbish TS. Diaphyseal aclasis (multiple exostoses) on Guam. Am J Hum Genet. 1961;13:340–347.13754517
   PubMed Web of Science ®Google Scholar
• Stocks P, Barrington A. Hereditary Disorders of Bone Development. Vol. 3. Treasury of Human Inheritance. London: Cambridge University Press; 1925.
   Google Scholar
• Terry Canale S. Campbell’s Operative Orthopaedics. St.louis: Mosby; 2005.
   Google Scholar
• Uchida K, Kurihara Y, Sekiguchi S, et al. Spomtaneous haemotorax caused by costal exostosis. Eur Respir J. 1997;10:735–736.9073015
   PubMed Web of Science ®Google Scholar
• D’Ambrosi RD, Ragone V, Caldarini C, et al. The impact of hereditary multiple exostoses on quality of life, satisfaction, global health status, and pain. Arch Orthop Trauma Surg. 2017;137(2):209–215. doi:10.1007/s00402-016-2608-427933382
   PubMed Web of Science ®Google Scholar
• D’Ambrosi RD, Caldarini C, Ragone V, Facchini RM. Eff ect of multiple hereditary exostoses on sports activity in children. J Orthop. 2018;15(4):927–930. doi:10.1016/j.jor.2018.08.02930190634
   PubMed Web of Science ®Google Scholar
• Chhina H 1, Davis JC, Alvarez CM. Health-related quality of life in people with hereditary multiple exostoses. J Pediatr Orthop. 2012;32(2):210–214. doi:10.1097/BPO.0b013e31823ee31c22327458
   PubMedGoogle Scholar
• Porter DE, Lonie L, Fraser M, et al. Severity of disease and risk of malignant change in hereditary multiple exostoses. A genotype phenotype study. J Bone Joint Surg Br. 2004;86:1041e6.15446535
   PubMedGoogle Scholar
• Kumar A, Jain VK, Bharadwaj M, et al. Ollier disease: pathogenesis, diagnosis, and management. Orthopedics. 2015;38(6):e497–e506. doi:10.3928/01477447-20150603-5826091223
   PubMed Web of Science ®Google Scholar
• Shapiro F, Simon S, Glimcher HJ. Hereditary multiple exostoses. Anthropometric, roentgenographic, and clinical aspects. J Bone Joint Surg Am. 1979;61(6):815e24.225330
   PubMed Web of Science ®Google Scholar
• Colnot C, Lu C, Hu D, Helms JA. Distinguishing the contributions of the perichondrium, cartilage, and vascular endothelium to skeletal development. Dev Biol.2004;269:55–69. doi:10.1016/j.ydbio.2004.01.01115081357
   PubMed Web of Science ®Google Scholar
• Stickens D, Clines G, Burbee D, et al. The EXT2 multiple hereditary exostoses gene defines a family of putative tumor suppressor genes. Nat Genet. 1996;14:25–32. doi:10.1038/ng0996-258782816
   PubMed Web of Science ®Google Scholar
• Jamsheer A, Socha M, Sowińska-Seidler A, et al. Mutational screening of EXT1 and EXT2 genes in polish patients with hereditary multiple exostoses. J Appl Genet. 2014;55(2):183–188. doi:10.1007/s13353-014-0195-z24532482
   PubMed Web of Science ®Google Scholar
• Alvarez C, Tredwell S, De Vera M, et al. The genotype-phenotype correlation of hereditary multiple exostoses. Clin Genet. 2006;70:122–130. doi:10.1111/j.1399-0004.2006.00653.x16879194
   PubMed Web of Science ®Google Scholar
• Ishimaru D, Gotch M, Takayama S, et al. Large scale mutational analysis in the the EXT1 and EXT2 genes for Japanese patients with multiple osteochondromas. BMC Genet. 2016;17:52. doi:10.1186/s12863-016-0359-426961984
   PubMed Web of Science ®Google Scholar
• Cousminer DL, Arkader A, Voight BF, et al. Assesing the general population frequency of rare coding variants in the EXT1 and –ext2 genes previously implicated in herditary multiple exostoses. Bone. 2016;92:196–200. doi:10.1016/j.bone.2016.09.00527616605
   PubMed Web of Science ®Google Scholar
• Jennes I, Pedrini E, Zuntini M, et al. Multiple osteochondromas: mutation up-date and description of the multiple osteochondromas mutation database (MOdb). Hum Mutat. 2009;30(12):1620–1627. doi:10.1002/humu.v30:1219810120
   PubMed Web of Science ®Google Scholar
• Szuhai K, Jennes I, de Jong D, et al. Tiling resolution array-CGH shows that somatic mosaic deletion of the EXT gene is causative in EXT gene mutation negative multiple osteochondromas patients. Hum Mutat. 2011;32(2):E2036–E2049. doi:10.1002/humu.v32.221280143
   PubMed Web of Science ®Google Scholar
• Zuntini M, Pedrini E, Parra A, et al. Genetic models of osteochondroma onset and neoplastic progression : evidence for mechanisms alternative to EXT genes inactivation. Oncogene. 2010;29(26):3827–3834. doi:10.1038/onc.2010.13520418910
   PubMed Web of Science ®Google Scholar
• Jones KB, Piombo V, Searby C, et al. A mouse model of osteochondromagenesis from clonal inactivation of Ext1 in chondrocytes. Proc Natl Acad Sci U S A. 2010;107:2054–2059. doi:10.1073/pnas.091087510720080592
   PubMed Web of Science ®Google Scholar
• Malini K, Gudi NS, Kutty AVM, et al. Mutational analysis of exostosin 1 and 2 genes in multiple osteochondroma. Indian J Pediatr. 2015;82(7):649–650. doi:10.1007/s12098-014-1675-125591329
   PubMed Web of Science ®Google Scholar
• Reijnders CM, Waaijer CJ, Hamilton A, et al. No haploinsufficiency but loss of heterozygosity for EXT in multiple osteochondromas. Am J Path. 2010;177:1946–1957. doi:10.2353/ajpath.2010.10029620813973
   PubMed Web of Science ®Google Scholar
• Sarrion P, Sangorrin A, Urreizti R, et al. Mutations in the EXT1 and EXT2 genes in Spanish patients with multiple osteochondromas. Sci Rep. 2013;3(1346):1–7. doi:10.1038/srep01346
   Web of Science ®Google Scholar
• Jones KB. Glycobiology and the growth plate: current concepts in multiple hereditary exostoses. J Pediatr Orthop.2011;31:577–586. doi:10.1097/BPO.0b013e31821c773821654469
   PubMed Web of Science ®Google Scholar
• Matsumoto K, Irie F, Mackem S, et al. A mouse model of chondrocyte-specific somatic mutation reveals a role for Ext1 loss of hereozygosity in multiple hereditary exostoses. Proc Natl Acad Sci U S A. 2010;107:10932–10937. doi:10.1073/pnas.091464210720534475
   PubMed Web of Science ®Google Scholar
• Busse- Wicher M, Wicher KB, Kusche-Gullberg M. The exostosin: family proteins with many functions. Matrix Biol. 2014;35:25–33. doi:10.1016/j.matbio.2013.10.00124128412
   PubMed Web of Science ®Google Scholar
• Jones KB, Pacifici M, Hilton MJ. Multiple hereditary exostoses (MHE): elucitading the pathogenesis of a rare skeletal disorder through interdisciplinary research. Connect Tissue Res. 2014;55(2):80–88. doi:10.3109/03008207.2013.86795724409815
   PubMed Web of Science ®Google Scholar
• McCormick C, Duncan G, Goustos KT, Tufaro F. The putative tumor suppressors EXT1 and EXT2 form a stable complex that accumulates in the golgi complex and catalyzes the synthesis of heparan sulfate. Proc Natl Acad Sci U S A.2000;97:668–673. doi:10.1073/pnas.97.2.66810639137
   PubMed Web of Science ®Google Scholar
• Mundy C, Bello A, Sgariglia F, Koyama E, Pacifici M. HhAntag, a hedgehog signaling antagonist, suppresses chondrogenesis and modulates canonical and non-canonical BMP signaling. J Cell Physiol. 2016;231:1033–1044. doi:10.1002/jcp.v231.526363135
   PubMed Web of Science ®Google Scholar
• Stickens D, Zak BM, Rougier N, et al. Mice deficient in Ext2 lack heparan sulfate and develpoe exostoses. Development. 2005;132:5055–5068. doi:10.1242/dev.0208816236767
   PubMed Web of Science ®Google Scholar
• Yoon BS, Pogue R, Ovchinnikov DA, et al. BMPs regulate multiple aspects of growth-plate chondrogenesis through opposing actions on FGF pathways. Development. 2006;133:4667–4678. doi:10.1242/dev.0268017065231
   PubMed Web of Science ®Google Scholar
• Billings PC, Pacifici M. Interactions of signaling proteins, growth factors and other proteins with heparan sulfate: mechanism and mysteries. Connect Tissue Res.2015;56:272–280. doi:10.3109/03008207.2015.104506626076122
   PubMed Web of Science ®Google Scholar
• Jochmann K, Bachvarova V, Vortkamp A. Reprint of: heparane sulfate as a regulator of endochondral ossification and osteochondroma development. Matrix Biol. 2014;35:239–247. doi:10.1016/j.matbio.2014.04.00124726293
   PubMed Web of Science ®Google Scholar
• Irie F, Badie-Mahdavi H, Yamaguchi Y. Autism-like socio-communicative deficits and stereotypies in mice lacking heparan sulfate. Proc Natl Acad Sci U S A. 2012;109:5052–5056. doi:10.1073/pnas.111788110922411800
   PubMed Web of Science ®Google Scholar
• Hennekam RC. Hereditary multiple exostoses. J Med Genet. 1991;28:262e268. doi:10.1136/jmg.28.4.2621856833
   PubMed Web of Science ®Google Scholar
• Jaffe ML. Heriditary multiple exostosis. Arch Pathol. 1943;36:335–357.
   Google Scholar
• Sugiura Y, Sugiura I, Iwata H. Heriditary multiple exostoses. Jpn J Hum Genet. 1976;21:149–167.
   Google Scholar
• Mordenti M, Ferrari E, Pedrini E, et al. Validation of a new multiple osteochondromas classification through switching neural networks. Am J Med Genet. 2013;161 A:556–560. doi:10.1002/ajmg.a.35819
   Web of Science ®Google Scholar
• Ali S, Kaplan S, Kaufman T, et al. Madelung deformity and madelung-type deformities: a review of the clinical and radiological characteristics. Pediatr Radiol. 2015;45:1856–1863. doi:10.1007/s00247-015-3390-026135644
   PubMed Web of Science ®Google Scholar
• Wang YZ, Park KW, Oh CS, et al. Developmental pattern of the hip in patients with hereditary multiple exostoses. BMC Musculoskelet Disord. 2015;16:54. doi:10.1186/s12891-015-0514-525888017
   PubMed Web of Science ®Google Scholar
• Vaishya R, Swami S, Vijay V, et al. Bilateral total hip arthroplasty in a young man with hereditary multiple exostoses. BMJ Case Rep. 2015;2015:bcr2014207853–bcr2014207853. doi:10.1136/bcr-2014-207853
   Google Scholar
• Clement ND, Porter DE. Can deformity of the knee and longitudinal growth of the leg be predicted in patients with hereditary multiple exostoses? A cross-sectional study. Knee. 2014;21:299–303. doi:10.1016/j.knee.2012.10.02923177660
   PubMed Web of Science ®Google Scholar
• Noonan KJ, Feinberg JR, Levenda A, et al. Natural history of multiple hereditary osteochondromatosis of the lower extremity and ankle. Pediatr Orthop. 2002;22:120–124. doi:10.1097/01241398-200201000-00025
   Google Scholar
• Matsumoto Y, Matsumoto K, Harimaya K, et al. Scoliosis in patients with multiple hereditary exostoses. J Bone Joint Surg Am. 2009;91:1942–1948. doi:10.2106/JBJS.H.0076219651953
   PubMed Web of Science ®Google Scholar
• Staal HM, Goud AL, van der Woude HJ, et al. Skeletal maturity of children with multiple ostechondromas: is diminished stature due to a systemic influence? J Child Orthop. 2015;9(5):397–402. doi:10.1007/s11832-015-0680-x26320759
   PubMedGoogle Scholar
• Rozeman LB, de Bruijn IH, Bacchini P, et al. Dedifferentiated peripheral chondrosarcomas: regulation of EXT-downstream molecules and differentiation related genes. Mod Path. 2009;22:1489–1498. doi:10.1038/modpathol.2009.12019734846
   PubMed Web of Science ®Google Scholar
• Marrero Barrera PA, Marrero Ortiz PB. Ewing sarcoma superimposed on a previuos ostechondroma in multiple ostechondromatosis. Orthopedics. 2014;37(4):e403–e406. doi:10.3928/01477447-20140401-6524762849
   PubMed Web of Science ®Google Scholar
• Goud A, de Lange J, Scholtes VA, et al. Pain physical and social functioning, and quality of life in individuals with multiple hereditary exostoses in the Nederlands: a national cohort study. J Bone Joint Surg Am. 2012;94:1013–1020. doi:10.2106/JBJS.K.0040622637207
   PubMed Web of Science ®Google Scholar
• Kok HK, Fitzgerald L, Campbell N, et al. Multimodality imaging features of hereditary multiple exostoses. Br J Radiol. 2013;86:20130398. doi:10.1259/bjr.2013039824004486
   PubMed Web of Science ®Google Scholar
• Northrup BE, Slat DF, Loomans RU, et al. The myriad of diseases that present with polyostotic bone lesions. Curr Probl Diagn Radiol. 2014;43(4):186–204. doi:10.1067/j.cpradiol.2014.01.00324948212
   PubMedGoogle Scholar
• Sonne-Holm E, Wong C, Sonne-Holm S. Multiple cartilaginous exostoses and development of chondrosarcomas – a systematic review. Dan Med J. 2014;61(9):A4895.25186537
   PubMed Web of Science ®Google Scholar
• Faruqi T, Dhawan N, Bahl J, et al. Molecular, phenotypic aspects and therapeutic horizons of rare genetic bone disorders. Biomed Res Int. 2014;2014:670842. doi:10.1155/2014/67084225530967
   PubMed Web of Science ®Google Scholar
• Cappuccio G, Genesio R, Ronga V, et al. Complex chromosomal rearrangements causing langer-giedion syndrome atypical phenotype: genotype-phenotype correlation and literature review. Am J Med Genet A. 2014;164A(3):753–759. doi:10.1002/ajmg.a.3632624357330
   PubMed Web of Science ®Google Scholar
• Fisher TJ, Williams N, Morris L, et al. Metachondromatosis: more than just multiple osteochondromas. J Child Orthop. 2013;7(6):455–464. doi:10.1007/s11832-013-0526-324432109
   PubMedGoogle Scholar
• Sciubba DM, Macki M, Bydon M, et al. Long-term outcomes in primary spinal osteochondroma: a multicenter study of 27 patients. J Neurosurg Spine. 2015;22(6):582–588. doi:10.3171/2014.10.SPINE1450125793467
   PubMed Web of Science ®Google Scholar
• Wu Q, Xiao BO, Li LI, Feng LI. Atypical teratoid/rhabdoid tumor with hereditary multiple exostoses in an 18-year-old male : a case report. Oncol Lett. 2015;10:1561–1564. doi:10.3892/ol.2015.338926622709
   PubMed Web of Science ®Google Scholar
• Alvarez CM, De Vera MA, Heslip TR, et al. Evaluation of the anatomic burden of patients with hereditary multiple exostoses. Clin Orthop Relat Res. 2007;462:73–79. doi:10.1097/BLO.0b013e3181334b5117589361
   PubMed Web of Science ®Google Scholar
• Woodside JC, Ganey T, Gaston RG. Multiple osteochondroma of the hand : initial and long-term follow-up study. Hand. 2015;10:616–620. doi:10.1007/s11552-015-9775-626568714
   PubMedGoogle Scholar
• Darilek S, Wicklund C, Novy D, et al. Hereditary multiple exostosis and pain. J Pediatr Orthop. 2005;25(3):369–376. doi:10.1097/01.bpo.0000150813.18673.ad15832158
   PubMed Web of Science ®Google Scholar
• Roach JW, Klatt JWB, Faulkner ND. Involvement of the spine in patients with multiple hereditary exostoses. J Bone Joint Surg Am. 2009;91:1942–1948. doi:10.2106/JBJS.H.0076219651953
   PubMed Web of Science ®Google Scholar
• Ashraf A, Larson AN, Ferski G, Guidera KJ. Spinal stenosis frequent in children with multiple hereditary exostoses. J Child Orthop. 2013;7:183–194. doi:10.1007/s11832-013-0484-924432077
   PubMedGoogle Scholar
• Kivioja A, Ervasti H, Kinnunen J, et al. Chondrosarcoma in a family with multiple hereditary ¨exostoses. J Bone Joint Surg B. 2000;82(2):261–266. doi:10.1302/0301-620X.82B2.10139
   Google Scholar
• Huegel J, Enomoto-Iwamoto M, Sgariglia F, et al. Heparanase stimulates chondrogenesis and is up-regulated in human ectopic cartilage. a mechanism possibly involved in hereditary multiple exostoses. Am J Pathol. 2015;185:1676–1685. doi:10.1016/j.ajpath.2015.02.01425863260
   PubMed Web of Science ®Google Scholar
• Huegel J, Mundy C, Sgariglia F, et al. Perichondrium phenotype and border function are regulated by Ext1 and heparan sulfate in developing long bones: a mechanism likely deranged in hereditary multiple exostoses. Dev Biol. 2013;377(1):100–112. doi:10.1016/j.ydbio.2013.02.00823458899
   PubMed Web of Science ®Google Scholar
• Sinha S, Mundy C, Bechtold T, et al. Unsuspected osteochondroma-like outgrowths in the cranial base of hereditary multiple exostoses patients and modeling and treatment with a BMP antagonist in mice. PLoS Genet. 2017;13(4):e1006742. doi:10.1371/journal.pgen.100674228445472
   PubMed Web of Science ®Google Scholar
• Inubushi T, Lemire I, Irie F, et al. Palovarotene inhibits osteochondroma formation in a mouse model of multiple hereditary exostoses. J Bone Miner Res. 2018;33(4):658–666. doi:10.1002/jbmr.334129120519
   PubMed Web of Science ®Google Scholar
• Shimono K, Tung WE, Macolino C, et al. Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor γ agonists. Nat Med. 2011;17(4):454–460. doi:10.1038/nm.233421460849
   PubMed Web of Science ®Google Scholar
• D’Ambrosi RD, Barbato A, Caldarini C, Biancardi E, Facchini RM, Ambrosi RD. Gradual ulnar lengthening in children with multiple exostoses and radial head dislocation : results at skeletal maturity. J Child Orthop. 2016;10(2):127–133. doi:10.1007/s11832-016-0718-826910403
   PubMedGoogle Scholar
• Jager M, Westhoff B, Portier S, et al. Clinical outcome and genotype in patients with hereditary multiple exostoses. Clinical outcome and genotype in patients with hereditary multiple exostoses. J Orthop Res. 2007;25:1541–1551. doi:10.1002/(ISSN)1554-527X17676624
   PubMed Web of Science ®Google Scholar
• Wirganowicz PZ, Watts HG. Surgical risk for elective excision of benign exostoses. J Pediatr Orthop. 1997;17:455–459. doi:10.1097/01241398-199707000-000089364382
   PubMed Web of Science ®Google Scholar
• Passanise AM, Mehlman CT, Wall EJ, et al. Radiographic evidence of regression of a solitary osteochondroma: a report of 4 cases and a literature review. J Pediatr Orthop. 2011;31:312–316. doi:10.1097/BPO.0b013e31820fc67621415692
   PubMed Web of Science ®Google Scholar
• Bassett GS, Cowell HR. Metachondromatatosis. J Bone Joint Surg Am. 1985;67:811–814. doi:10.2106/00004623-198567050-000223873457
   PubMed Web of Science ®Google Scholar
• Kang S, Kim JY, Park SS. Outcomes of hemiepiphyseal stapling for genu valgum deformities in patients with multiple hereditary exostoses: a comparative study of patients with deformities of idiopathic cause. J Pediatr Orthop. 2017;37:265–271. doi:10.1097/BPO.000000000000062826296227
   PubMed Web of Science ®Google Scholar
• Kelly JP, James MA. Radiographic outcomes of hemiepiphyseal stapling for distal radius deformity due to multiple hereditary exostoses. J Pediatr Orthop. 2016;36:42–47. doi:10.1097/BPO.000000000000039425633611
   PubMed Web of Science ®Google Scholar
• Lee DY, Kim JI, Song MH, et al. Fibular lengthening for the management of translational talus instability in hereditary multiple exostoses patients. J Pediatr Orthop. 2014;34:726–732. doi:10.1097/BPO.000000000000018124705345
   PubMed Web of Science ®Google Scholar
• Guindani N, Eberhardt O, Wirth T, et al. Surgical dislocation for pediatric and adolescent hip deformity: clinical and radiographical results at 3 years follow-up. Arch Orthop Trauma Surg. 2017;137:471–479. doi:10.1007/s00402-017-2644-828197752
   PubMed Web of Science ®Google Scholar
• Pacifici M. Hereditary multiple exostoses: new insights into pathogenesis, clinical complications and potential treatments. Curr Osteoporos Rep. 2017;15(3):142–152. doi:10.1007/s11914-017-0355-228466453
   PubMed Web of Science ®Google Scholar
• Beltrami G, Ristori G, Scoccianti G, Tamburini A, Capanna R. Heriditary multiple exostoses: a review of clinical appearance and metabolic pattern. Clin Cases Miner Bone Metab. 2016;13(2):110–118. doi:10.11138/ccmbm/2016.13.2.11027920806
   PubMedGoogle Scholar
• Koyoma E, Young B, Nagayama M, et al. Conditional Kif3a ablation causes abnormal hedgehog signaling topography, growth plate dysfunction, and excessive bone and cartilage formation during mouse skeletogenesis. Development. 2007;134:2159–2169. doi:10.1242/dev.00158617507416
   PubMed Web of Science ®Google Scholar