Skip to main content
SpringerLink
Log in

Genetische Skeletterkrankungen und Entwicklungsstörungen

  • Chapter
  • First Online:
Pathologie

Part of the book series: Pathologie ((PATHOL))

  • 6056 Accesses

Zusammenfassung

In einem allgemeinen Abschnitt werden diagnostische Schritte erläutert, die für eine Zuordnung von konstitutionellen Skeletterkrankungen in diagnostische Gruppen erforderlich sind. Die Klassifikation der Skelettentwicklungsstörungen, die zunehmend auf der Basis molekulargenetischer Befunde erfolgt, wird zusammenfassend aufgeführt. In einem speziellen Abschnitt werden ausgewählte Skelettdysplasien und andere genetisch bedingte Skeletterkrankungen hinsichtlich Epidemiologie, Pathogenese, Klinik, Radiologie und Morphologie dargestellt.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 469.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Literatur

  1. Albagha OM et al (2010) Genome-wide association study identifies variants at CSF1, OPTN and TNFRSF11A as genetic risk factors for Paget’s disease of bone. Nat Genet 42:520–524

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  2. Barvencik F et al (2014) CLCN7 and TCIRG1 mutations differentially affect bone matrix mineralization in osteopetrotic individuals. J Bone Miner Res 29:982–991

    Article  CAS  PubMed  Google Scholar 

  3. Ben-Asher E et al (2005) LEMD3: the gene responsible for bone density disorders (osteopoikilosis). Isr Med Assoc J 7:273–274

    PubMed  Google Scholar 

  4. Benli IT et al (1992) Epidemiological, clinical and radiological aspects of osteopoikilosis. J Bone Joint Surg Br 74:504–506

    CAS  PubMed  Google Scholar 

  5. Beyens G et al (2007) Identification of sex-specific associations between polymorphisms of the osteoprotegerin gene, TNFRSF11B, and Paget’s disease of bone. J Bone Miner Res 22:1062–1071

    Article  CAS  PubMed  Google Scholar 

  6. Brown RR et al (2000) Melorheostosis: case report with radiologic-pathologic correlation. Skeletal Radiol 29:548–552

    Article  CAS  PubMed  Google Scholar 

  7. Campbell CJ et al (1968) Melorheostosis. A report of the clinical, roentgenographic, and pathological findings in fourteen cases. J Bone Joint Surg Am 50:1281–1304

    CAS  PubMed  Google Scholar 

  8. Cavey JR et al (2006) Loss of ubiquitin binding is a unifying mechanism by which mutations of SQSTM1 cause Paget’s disease of bone. Calcif Tissue Int 78:271–277

    Article  CAS  PubMed  Google Scholar 

  9. Cheung MS et al (2008) Osteogenesis Imperfecta: update on presentation and management. Rev Endocr Metab Disord 9:153–160

    Article  PubMed  Google Scholar 

  10. Chong B et al (2003) Idiopathic hyperphosphatasia and TNFRSF11B mutations: relationships between phenotype and genotype. J Bone Miner Res 18:2095–2104

    Article  CAS  PubMed  Google Scholar 

  11. Chung PY et al (2010) The majority of the genetic risk for Paget’s disease of bone is explained by genetic variants close to the CSF1, OPTN, TM7SF4, and TNFRSF11A genes. Hum Genet 128:615–626

    Article  PubMed  Google Scholar 

  12. Chung PY et al (2011) Indications for a genetic association of a VCP polymorphism with the pathogenesis of sporadic Paget’s disease of bone, but not for TNFSF11 (RANKL) and IL-6 polymorphisms. Mol Genet Metab 103:287–292

    Article  CAS  PubMed  Google Scholar 

  13. Chung PY et al (2010) Genetic variation in the TNFRSF11A gene encoding RANK is associated with susceptibility to Paget’s disease of bone. J Bone Miner Res 25:2592–2605

    Article  PubMed  Google Scholar 

  14. Chung PY et al (2012) Paget’s disease of bone: evidence for complex pathogenetic interactions. Semin Arthritis Rheum 41:619–641

    Article  CAS  PubMed  Google Scholar 

  15. Cleiren E et al (2001) Albers-Schonberg disease (autosomal dominant osteopetrosis, type II) results from mutations in the ClCN7 chloride channel gene. Hum Mol Genet 10:2861–2867

    Article  CAS  PubMed  Google Scholar 

  16. Couto AR et al (2007) A novel LEMD3 mutation common to patients with osteopoikilosis with and without melorheostosis. Calcif Tissue Int 81:81–84

    Article  CAS  PubMed  Google Scholar 

  17. Daroszewska A et al (2004) Susceptibility to Paget’s disease of bone is influenced by a common polymorphic variant of osteoprotegerin. J Bone Miner Res 19:1506–1511

    Article  CAS  PubMed  Google Scholar 

  18. Davie M et al (1999) Paget’s disease of bone: A review of 889 patients. Bone 24:11S–12S

    Article  CAS  PubMed  Google Scholar 

  19. Delling G (1997) Skelettsystem. In: Remmele W (Hrsg) Pathologie, 2. Aufl. Springer, Berlin

    Google Scholar 

  20. Edouard T et al (2011) Relationship between vitamin D status and bone mineralization, mass, and metabolism in children with osteogenesis imperfecta: histomorphometric study. J Bone Miner Res 26:2245–2251

    Article  CAS  PubMed  Google Scholar 

  21. Eekhoff E et al (2004) Familial Paget’s disease in The Netherlands: occurrence, identification of new mutations in the sequestosome 1 gene, and their clinical associations. Arthritis Rheum 50:1650–1654

    Article  CAS  PubMed  Google Scholar 

  22. Farahmand P et al (2011) Epidemiologie des Morbus Paget. Osteologie 20:114–118

    Google Scholar 

  23. Feng X et al (2011) Disorders of bone remodeling. Annu Rev Pathol 6:121–145

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  24. Frattini A et al (2000) Defects in TCIRG1 subunit of the vacuolar proton pump are responsible for a subset of human autosomal recessive osteopetrosis. Nat Genet 25:343–346

    Article  CAS  PubMed  Google Scholar 

  25. Frenzel L et al (2012) Ivory vertebra and systemic mastocytosis. Joint Bone Spine 79:319–321

    Article  PubMed  Google Scholar 

  26. Gamage NM et al (2013) Giant-cell-rich pseudotumour in Paget’s disease. Skeletal Radiol 42:595–599

    Article  CAS  PubMed  Google Scholar 

  27. Gebhart M et al (1998) Paget’s disease of bone complicated by giant cell tumor. Clin Orthop Relat Res 352:187–193

    PubMed  Google Scholar 

  28. Gianfrancesco F et al (2013) Giant cell tumor occurring in familial Paget’s disease of bone: report of clinical characteristics and linkage analysis of a large pedigree. J Bone Miner Res 28:341–350

    Article  CAS  PubMed  Google Scholar 

  29. Glorieux FH et al (2013) Osteogenesis imperfecta, an ever-expanding conundrum. J Bone Miner Res 28:1519–1522

    Article  PubMed  Google Scholar 

  30. Gonen KA et al (2013) Infantile osteopetrosis with superimposed rickets. Pediatr Radiol 43:189–195

    Article  PubMed  Google Scholar 

  31. Grabner B et al (2001) Age- and genotype-dependence of bone material properties in the osteogenesis imperfecta murine model (oim). Bone 29:453–457

    Article  CAS  PubMed  Google Scholar 

  32. Greenspan A et al (1999) Bone dysplasia series. Melorheostosis: review and update. Can Assoc Radiol J 50:324–330

    CAS  PubMed  Google Scholar 

  33. Hansen MF et al (2006) Osteosarcoma in Paget’s disease of bone. J Bone Miner Res 21(2):58–63

    Article  Google Scholar 

  34. Hellemans J et al (2006) Germline LEMD3 mutations are rare in sporadic patients with isolated melorheostosis. Hum Mutat 27:290

    Article  PubMed  Google Scholar 

  35. Hocking LJ et al (2012) Autophagy: a new player in skeletal maintenance? J Bone Miner Res 27:1439–1447

    Article  CAS  PubMed  Google Scholar 

  36. Homan EP et al (2011) Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res 26:2798–2803

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  37. Hughes AE et al (2000) Mutations in TNFRSF11A, affecting the signal peptide of RANK, cause familial expansile osteolysis. Nat Genet 24:45–48

    Article  CAS  PubMed  Google Scholar 

  38. Huvos AG et al (1983) Osteogenic sarcoma associated with Paget’s disease of bone. Cancer 52:1489–1495

    Article  CAS  PubMed  Google Scholar 

  39. Jattiot F et al (1999) Fourteen cases of sarcomatous degeneration in Paget’s disease. J Rheumatol 26:150–155

    CAS  PubMed  Google Scholar 

  40. Kaplan FS et al (1993) Osteopetrorickets. The paradox of plenty. Pathophysiology and treatment. Clin Orthop Relat Res 294:64–78

    PubMed  Google Scholar 

  41. Karakida K et al (2010) Multiple giant cell tumors in maxilla and skull complicating Paget’s disease of bone. Tokai J Exp Clin Med 35:112–117

    PubMed  Google Scholar 

  42. Kessler HB et al (1983) Vascular anomalies in association with osteodystrophies – a spectrum. Skeletal Radiol 10:95–101

    Article  CAS  PubMed  Google Scholar 

  43. Kimonis VE et al (2008) VCP disease associated with myopathy, Paget disease of bone and frontotemporal dementia: review of a unique disorder. Biochim Biophys Acta 1782:744–748

    Article  CAS  PubMed  Google Scholar 

  44. Klein MJ et al (2011) Inherited and developmental bone diseases. In: Klein MJ (Hrsg) Non-neoplastic diseases of bones and joints, 1. Aufl. American Registry of Pathology, Washington, DC

    Google Scholar 

  45. Kornak U et al (2001) Loss of the ClC-7 chloride channel leads to osteopetrosis in mice and man. Cell 104:205–215

    Article  CAS  PubMed  Google Scholar 

  46. Laederich MB et al (2010) Achondroplasia: pathogenesis and implications for future treatment. Curr Opin Pediatr 22:516–523

    Article  PubMed  Google Scholar 

  47. Lagier R et al (1984) Osteopoikilosis: a radiological and pathological study. Skeletal Radiol 11:161–168

    Article  CAS  PubMed  Google Scholar 

  48. Laine CM et al (2013) WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N Engl J Med 368:1809–1816

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  49. Land C et al (2009) Osteogenesis imperfecta. Pathogenese, klinische Aspekte und medikamentöse Therapie. Osteologie 18:285–292

    Google Scholar 

  50. Laurin N et al (2001) Paget disease of bone: mapping of two loci at 5q35-qter and 5q31. Am J Hum Genet 69:528–543

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  51. Laurin N et al (2002) Recurrent mutation of the gene encoding sequestosome 1 (SQSTM1/p62) in Paget disease of bone. Am J Hum Genet 70:1582–1588

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  52. Layfield R et al (2004) Structural and functional studies of mutations affecting the UBA domain of SQSTM1 (p62) which cause Paget’s disease of bone. Biochem Soc Trans 32:728–730

    Article  CAS  PubMed  Google Scholar 

  53. Martinez-Frias ML et al (2010) Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A 152A:245–255

    Article  CAS  PubMed  Google Scholar 

  54. Michl W (2014) Konstitutionelle Skelettentwicklungsstörungen. In: Bohndorf K, Imhof H, Wörtler K (Hrsg) Radiologische Diagnostik der Knochen und Gelenke, 3. Aufl. Thieme, Stuttgart

    Google Scholar 

  55. Mirra JM et al (1995) Paget’s disease of bone: Review with emphasis on radiologic features, part I. Skeletal Radiol 24:163–171

    CAS  PubMed  Google Scholar 

  56. Mirra JM et al (1995) Paget’s disease of bone: Review with emphasis on radiologic features, part II. Skeletal Radiol 24:173–184

    CAS  PubMed  Google Scholar 

  57. Morales-Piga AA et al (1995) Frequency and characteristics of familial aggregation of Paget’s disease of bone. J Bone Miner Res 10:663–670

    Article  CAS  PubMed  Google Scholar 

  58. Morello R et al (2006) CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell 127:291–304

    Article  CAS  PubMed  Google Scholar 

  59. Morissette J et al (2006) Sequestosome 1: mutation frequencies, haplotypes, and phenotypes in familial Paget’s disease of bone. J Bone Miner Res 21 Suppl 2:38–44

    Article  Google Scholar 

  60. Mumm S et al (2007) Deactivating germline mutations in LEMD3 cause osteopoikilosis and Buschke-Ollendorff syndrome, but not sporadic melorheostosis. J Bone Miner Res 22:243–250

    Article  CAS  PubMed  Google Scholar 

  61. Murray RO et al (1979) Melorheostosis and the sclerotomes: a radiological correlation. Skeletal Radiol 4:57–71

    Article  CAS  PubMed  Google Scholar 

  62. Nagai R et al (1997) Renal tubular acidosis and osteopetrosis with carbonic anhydrase II deficiency: pathogenesis of impaired acidification. Pediatr Nephrol 11:633–636

    Article  CAS  PubMed  Google Scholar 

  63. Nakatsuka K et al (2003) Phenotypic characterization of early onset Paget’s disease of bone caused by a 27-bp duplication in the TNFRSF11A gene. J Bone Miner Res 18:1381–1385

    Article  CAS  PubMed  Google Scholar 

  64. Neale SD et al (2002) The influence of serum cytokines and growth factors on osteoclast formation in Paget’s disease. QJM 95:233–240

    Article  CAS  PubMed  Google Scholar 

  65. Pangrazio A et al (2012) RANK-dependent autosomal recessive osteopetrosis: characterization of five new cases with novel mutations. J Bone Miner Res 27:342–351

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  66. Patoine A et al (2014) Topological mapping of bril reveals a type II orientation and effects of osteogenesis imperfecta mutations on its cellular destination. J Bone Miner Res 29:2004–2016

    Article  CAS  PubMed  Google Scholar 

  67. Perez RJ et al (2014) Osteopoikilosis with involvement of the spine, an atypical presentation. Reumatol Clin 10:127–129

    Article  Google Scholar 

  68. Pfeifer M et al (2011) Röntgendiagnostik des Morbus Paget. Osteologie 20:128–133

    Google Scholar 

  69. Ralston SH et al (2012) Pathogenesis of Paget disease of bone. Calcif Tissue Int 91:97–113

    Article  CAS  PubMed  Google Scholar 

  70. Rauch F et al (2004) Osteogenesis imperfecta. Lancet 363:1377–1385

    Article  CAS  PubMed  Google Scholar 

  71. Rauch F et al (2000) Static and dynamic bone histomorphometry in children with osteogenesis imperfecta. Bone 26:581–589

    Article  CAS  PubMed  Google Scholar 

  72. Scharla S (2011) Morbus Paget des Knochens. Klinische Symptomatik und Laborveränderungen. Osteologie 20:109–113

    Google Scholar 

  73. Seefried L et al (2011) Pathogenese des Morbus Paget. Osteologie 20:119–127

    Google Scholar 

  74. Semler O et al (2013) Genetische Ursachen und therapeutische Optionen bei Osteoporose im Kindes- und Jugendalter. Osteologie 22:93–99

    Google Scholar 

  75. Sillence DO et al (1979) Genetic heterogeneity in osteogenesis imperfecta. J Med Genet 16:101–116

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  76. Sly WS et al (1983) Carbonic anhydrase II deficiency identified as the primary defect in the autosomal recessive syndrome of osteopetrosis with renal tubular acidosis and cerebral calcification. Proc Natl Acad Sci U S A 80:2752–2756

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  77. Sobacchi C et al (2001) The mutational spectrum of human malignant autosomal recessive osteopetrosis. Hum Mol Genet 10:1767–1773

    Article  CAS  PubMed  Google Scholar 

  78. Sobacchi C et al (2013) Osteopetrosis: genetics, treatment and new insights into osteoclast function. Nat Rev Endocrinol 9:522–536

    Article  CAS  PubMed  Google Scholar 

  79. Sparks AB et al (2001) Mutation screening of the TNFRSF11A gene encoding receptor activator of NF kappa B (RANK) in familial and sporadic Paget’s disease of bone and osteosarcoma. Calcif Tissue Int 68:151–155

    Article  CAS  PubMed  Google Scholar 

  80. van Staa TP et al (2002) Incidence and natural history of Paget’s disease of bone in England and Wales. J Bone Miner Res 17:465–471

    Article  PubMed  Google Scholar 

  81. Van WL et al (2003) Six novel missense mutations in the LDL receptor-related protein 5 (LRP5) gene in different conditions with an increased bone density. Am J Hum Genet 72:763–771

    Article  Google Scholar 

  82. Visconti MR et al (2010) Mutations of SQSTM1 are associated with severity and clinical outcome in paget disease of bone. J Bone Miner Res 25:2368–2373

    Article  CAS  PubMed  Google Scholar 

  83. Warman ML et al (2011) Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A 155A:943–968

    Article  PubMed  Google Scholar 

  84. Watts GD et al (2004) Inclusion body myopathy associated with Paget disease of bone and frontotemporal dementia is caused by mutant valosin-containing protein. Nat Genet 36:377–381

    Article  CAS  PubMed  Google Scholar 

  85. Whyte MP et al (2002) Expansile skeletal hyperphosphatasia is caused by a 15-base pair tandem duplication in TNFRSF11A encoding RANK and is allelic to familial expansile osteolysis. J Bone Miner Res 17:26–29

    Article  CAS  PubMed  Google Scholar 

  86. Whyte MP et al (2004) Heritable disorders of the RANKL/OPG/RANK signaling pathway. J Musculoskelet Neuronal Interact 4:254–267

    CAS  PubMed  Google Scholar 

  87. Whyte MP et al (2002) Osteoprotegerin deficiency and juvenile Paget’s disease. N Engl J Med 347:175–184

    Article  CAS  PubMed  Google Scholar 

  88. Zhang Y et al (2009) Novel and recurrent germline LEMD3 mutations causing Buschke-Ollendorff syndrome and osteopoikilosis but not isolated melorheostosis. Clin Genet 75:556–561

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Sarkomzentrum Berlin-Brandenburg, Institut für Pathologie, MVZ am Helios Klinikum Emil von Behring, Walterhöferstr. 11, 14165, Berlin, Deutschland

    Mathias Werner PD Dr. med.

Authors
  1. Mathias Werner PD Dr. med.
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mathias Werner PD Dr. med. .

Editor information

Editors and Affiliations

  1. Abt. Nephropathologie, Pathologisches Institut Universität Erlangen-Nürnberg, Erlangen, Germany

    Kerstin Amann

  2. Klinisches Institut für Pathologie, Medizinische Universität Wien Allg. Krankenhaus der Stadt Wien, Wien, Austria

    Renate Kain

  3. Konsultationszentrum für Pankreas- und Endokrine Tumoren, Institut für Pathologie, Ismaninger Str. 22, 81675, Technische Universität München Klinikum rechts der Isar, München, Germany

    Günter Klöppel

Rights and permissions

Reprints and permissions

Copyright information

© 2016 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Werner, M. (2016). Genetische Skeletterkrankungen und Entwicklungsstörungen. In: Amann, K., Kain, R., Klöppel, G. (eds) Pathologie. Pathologie. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-04566-0_42

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-04566-0_42

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-04565-3

  • Online ISBN: 978-3-642-04566-0

  • eBook Packages: Medicine (German Language)

Publish with us

Policies and ethics

Search

Navigation