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Classification of osteogenesis imperfecta

Klassifikation der Osteogenesis imperfecta

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Summary

Osteogenesis imperfecta (OI) is an extremely heterogeneous group of heritable connective tissue disorders. Most of the affected patients carry autosomal dominant mutations in the genes encoding for collagen type I, the most abundant protein of the bone extracellular matrix. The resulting phenotypes are extremely broad and have been classified by Sillence and colleagues into four groups according to clinical, radiological and genetic criteria.

More recently, proteins have been described that interact directly or indirectly with collagen biosynthesis and their deficiency result in rare forms of mostly autosomal recessive OI sharing phenotypic features of ‘classical’ types but lacking primary defects in type I collagen. Consequently the Sillence classification has been gradually expanded to include novel forms based on the underlying mutations. The goal of this article is to revisit the actual OI classification and to outline current approaches in categorizing the disorder.

Zusammenfassung

Osteogenesis imperfecta (OI) ist eine äußerst heterogene Gruppe von erblichen Erkrankungen des Bindegewebes. Die meisten der betroffenen Patienten sind Träger dominanter Mutationen in den Genen für Kollagen Typ I, dem häufigsten Protein der extrazellulären Matrix. Die sich daraus ergebenden Phänotypen sind sehr vielfältig und wurden von Sillence und Kollegen in vier Gruppen entsprechend klinischen, radiologischen und genetischen Kriterien eingeteilt.

In den letzten Jahren wurden neue Proteine beschrieben, die direkt oder indirekt mit der Kollagenbiosynthese wechselwirken. Sehr seltene Mutationen, die Störungen in diesen Proteinen hervorrufen, führen in der Regel zu autosomal-rezessiven Sonderformen mit einem ähnlichen klinischen Bild wie in den „klassischen“ Formen von OI, aber ohne primären Kollagendefekt. Deshalb wurde die Sillence Klassifikation schrittweise erweitert, um auch diese neuen Formen zu berücksichtigen, die durch ihre Mutation definiert sind. Das Ziel dieses Artikels ist es, den derzeitigen Stand der OI Klassifikation zu präsentieren und zu diskutieren.

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References

  1. Weil UH. Osteogenesis imperfecta: historical background. Clin Orthop Relat Res. 1981;159:6–10.

    PubMed  Google Scholar 

  2. Baljet B. Aspects of the history of osteogenesis imperfecta (Vrolik’s syndrome). Ann Anat. 2002;184:1–7.

    Article  CAS  PubMed  Google Scholar 

  3. De Rooy L, Knepper S. Forces of form: the Vrolik museum. Amsterdam; 2009.

  4. O’Riordan JL, Bijvoet OL. Rickets before the discovery of vitamin D. Bonekey Rep. 2014;3:478.

    PubMed Central  PubMed  Google Scholar 

  5. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979;16:101–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  6. Chu ML, Williams CJ, Pepe G, Hirsch JL, Prockop DJ, Ramirez F. Internal deletion in a collagen gene in a perinatal lethal form of osteogenesis imperfecta. Nature. 1983;304:78–80.

    Article  CAS  PubMed  Google Scholar 

  7. Forlino A, Cabral WA, Barnes AM, Marini JC. New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol. 2011;7:540–57.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  8. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014;164A:1470–81.

    Article  PubMed  Google Scholar 

  9. Rauch F, Lalic L, Roughley P, Glorieux FH. Genotype-phenotype correlations in nonlethal osteogenesis imperfecta caused by mutations in the helical domain of collagen type I. Eur J Hum Genet. 2010;18:642–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  10. Semler O, Cheung MS, Glorieux FH, Rauch F. Wormian bones in osteogenesis imperfecta: correlation to clinical findings and genotype. Am J Med Genet A. 2010;152 A:1681–7.

    Article  Google Scholar 

  11. Rauch F, Glorieux FH. Osteogenesis imperfecta. Lancet. 2004;363:1377–85.

    Article  CAS  PubMed  Google Scholar 

  12. Bishop N. Characterising and treating osteogenesis imperfecta. Early Hum Dev. 2010;86:743–6.

    Article  PubMed  Google Scholar 

  13. van Dijk FS, Cobben JM, Kariminejad A, Maugeri A, Nikkels PG, van Rijn RR, Pals G. Osteogenesis Imperfecta: a review with clinical examples. Mol Syndromol. 2011;2:1–20.

    PubMed Central  PubMed  Google Scholar 

  14. Makareeva E, Aviles NA, Leikin S. Chaperoning osteogenesis: new protein-folding disease paradigms. Trends Cell Biol. 2011;21:168–76.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. Ishikawa Y, Bachinger HP. A molecular ensemble in the rER for procollagen maturation. Biochim Biophys Acta. 2013;1833:2479–91.

    Article  CAS  PubMed  Google Scholar 

  16. Avery NE, Bailey AJ. Restraining cross-links responsible for the mechanical properties of collagen fibers: natural and artificial. In: Fratzl P, editor. Collagen Structure and Mechanics. New-York: Springer; 2008. pp. 81–110.

    Chapter  Google Scholar 

  17. Eyre DR, Weis MA. Bone collagen: new clues to its mineralization mechanism from recessive osteogenesis imperfecta. Calcif Tissue Int. 2013;93:338–47.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  18. Morello R, Bertin TK, Chen Y, Hicks J, Tonachini L, Monticone M, Castagnola P, Rauch F, Glorieux FH, Vranka J, Bachinger HP, Pace JM, Schwarze U, Byers PH, Weis M, Fernandes RJ, Eyre DR, Yao Z, Boyce BF, Lee B. CRTAP is required for prolyl 3- hydroxylation and mutations cause recessive osteogenesis imperfecta. Cell. 2006;127:291–304.

    Article  CAS  PubMed  Google Scholar 

  19. Marini JC, Cabral WA, Barnes AM, Chang W. Components of the collagen prolyl 3-hydroxylation complex are crucial for normal bone development. Cell Cycle. 2007;6:1675–81.

    Article  CAS  PubMed  Google Scholar 

  20. Barnes AM, Chang W, Morello R, Cabral WA, Weis M, Eyre DR, Leikin S, Makareeva E, Kuznetsova N, Uveges TE, Ashok A, Flor AW, Mulvihill JJ, Wilson PL, Sundaram UT, Lee B, Marini JC. Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med. 2006;355:2757–64.

    Article  CAS  PubMed  Google Scholar 

  21. Baldridge D, Schwarze U, Morello R, Lennington J, Bertin TK, Pace JM, Pepin MG, Weis M, Eyre DR, Walsh J, Lambert D, Green A, Robinson H, Michelson M, Houge G, Lindman C, Martin J, Ward J, Lemyre E, Mitchell JJ, Krakow D, Rimoin DL, Cohn DH, Byers PH, Lee B. CRTAP and LEPRE1 mutations in recessive osteogenesis imperfecta. Hum Mutat. 2008;29:1435–42.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  22. van Dijk FS, Nesbitt IM, Zwikstra EH, Nikkels PG, Piersma SR, Fratantoni SA, Jimenez CR, Huizer M, Morsman AC, Cobben JM, van Roij MH, Elting MW, Verbeke JI, Wijnaendts LC, Shaw NJ, Hogler W, McKeown C, Sistermans EA, Dalton A, Meijers-Heijboer H, Pals G. PPIB mutations cause severe osteogenesis imperfecta. Am J Hum Genet. 2009;85:521–7.

    Article  PubMed Central  PubMed  Google Scholar 

  23. Pyott SM, Schwarze U, Christiansen HE, Pepin MG, Leistritz DF, Dineen R, Harris C, Burton BK, Angle B, Kim K, Sussman MD, Weis M, Eyre DR, Russell DW, McCarthy KJ, Steiner RD, Byers PH. Mutations in PPIB (cyclophilin B) delay type I procollagen chain association and result in perinatal lethal to moderate osteogenesis imperfecta phenotypes. Hum Mol Genet. 2011;20:1595–609.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  24. Schwarze U, Cundy T, Pyott SM, Christiansen HE, Hegde MR, Bank RA, Pals G, Ankala A, Conneely K, Seaver L, Yandow SM, Raney E, Babovic-Vuksanovic D, Stoler J, Ben-Neriah Z, Segel R, Lieberman S, Siderius L, Al-Aqeel A, Hannibal M, Hudgins L, McPherson E, Clemens M, Sussman MD, Steiner RD, Mahan J, Smith R, Anyane-Yeboa K, Wynn J, Chong K, Uster T, Aftimos S, Sutton VR, Davis EC, Kim LS, Weis MA, Eyre D, Byers PH. Mutations in FKBP10, which result in Bruck syndrome and recessive forms of osteogenesis imperfecta, inhibit the hydroxylation of telopeptide lysines in bone collagen. Hum Mol Genet. 2013;22:1–17.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Marini JC, Blissett AR. New genes in bone development: what’s new in osteogenesis imperfecta. J Clin Endocrinol Metab. 2013;98:3095–103.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  26. Glorieux FH, Moffatt P. Osteogenesis imperfecta, an ever-expanding conundrum. J Bone Miner Res. 2013;28:1519–22.

    Article  PubMed  Google Scholar 

  27. Plotkin H. Syndromes with congenital brittle bones. BMC Pediatr. 2004;4:16.

    Article  PubMed Central  PubMed  Google Scholar 

  28. Van Dijk FS, Pals G, Van Rijn RR, Nikkels PG, Cobben JM. Classification of osteogenesis imperfecta revisited. Eur J Med Genet. 2010;53:1–5.

    Article  PubMed  Google Scholar 

  29. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M, Mortier G, Mundlos S, Nishimura G, Rimoin DL, Robertson S, Savarirayan R, Sillence D, Spranger J, Unger S, Zabel B, Superti-Furga A. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011;155 A: 943–68.

    Article  CAS  PubMed Central  Google Scholar 

  30. Lazarus S, Moffatt P, Duncan EL, Thomas GP. A brilliant breakthrough in OI type V. Osteoporos Int. 2014;25:399–405.

    Article  CAS  PubMed  Google Scholar 

  31. Marini JC, Reich A, Smith SM. Osteogenesis imperfecta due to mutations in non-collagenous genes: lessons in the biology of bone formation. Curr Opin Pediatr. 2014;26:500–7.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Fahiminiya S, Majewski J, Al-Jallad H, Moffatt P, Mort J, Glorieux FH, Roschger P, Klaushofer K, Rauch F. Osteoporosis caused by mutations in PLS3: clinical and bone tissue characteristics. J Bone Miner Res. 2014;29:1805–14.

    Article  CAS  PubMed  Google Scholar 

  33. Rauch F, Moffatt P, Cheung M, Roughley P, Lalic L, Lund AM, Ramirez N, Fahiminiya S, Majewski J, Glorieux FH. Osteogenesis imperfecta type V: marked phenotypic variability despite the presence of the IFITM5 c.-14 C > T mutation in all patients. J Med Genet. 2013;50:21–4.

    Article  CAS  PubMed  Google Scholar 

  34. Homan EP, Rauch F, Grafe I, Lietman C, Doll JA, Dawson B, Bertin T, Napierala D, Morello R, Gibbs R, White L, Miki R, Cohn DH, Crawford S, Travers R, Glorieux FH, Lee B. Mutations in SERPINF1 cause osteogenesis imperfecta type VI. J Bone Miner Res. 2011;26:2798–803.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  35. Christiansen HE, Schwarze U, Pyott SM, AlSwaid A, Balwi M A, Alrasheed S, Pepin MG, Weis MA, Eyre DR, Byers PH. Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta. Am J Hum Genet. 2010;86:389–98.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  36. Barnes AM, Cabral WA, Weis M, Makareeva E, Mertz EL, Leikin S, Eyre D, Trujillo C, Marini JC. Absence of FKBP10 in recessive type XI osteogenesis imperfecta leads to diminished collagen cross-linking and reduced collagen deposition in extracellular matrix. Hum Mutat. 2012;33:1589–98.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  37. Puig-Hervas MT, Temtamy S, Aglan M, Valencia M, Martinez-Glez V, Ballesta-Martinez MJ, Lopez-Gonzalez V, Ashour AM, Amr K, Pulido V, Guillen-Navarro E, Lapunzina P, Caparros-Martin JA, Ruiz-Perez VL. Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome–osteogenesis imperfecta phenotypic spectrum. Hum Mutat. 2012;33:1444–9.

    Article  CAS  PubMed  Google Scholar 

  38. Hoyer-Kuhn H, Semler O, Schoenau E, Roschger P, Klaushofer K, Rauch F. Hyperosteoidosis and hypermineralization in the same bone: bone tissue analyses in a boy with a homozygous BMP1 mutation. Calcif Tissue Int. 2013;93:565–70.

    Article  CAS  PubMed  Google Scholar 

  39. Lapunzina P, Aglan M, Temtamy S, Caparros-Martin JA, Valencia M, Leton R, Martinez-Glez V, Elhossini R, Amr K, Vilaboa N, Ruiz-Perez VL. Identification of a frameshift mutation in osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet. 2010;87:110–4.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  40. Laine CM, Joeng KS, Campeau PM, Kiviranta R, Tarkkonen K, Grover M, Lu JT, Pekkinen M, Wessman M, Heino TJ, Nieminen-Pihala V, Aronen M, Laine T, Kroger H, Cole WG, Lehesjoki AE, Nevarez L, Krakow D, Curry CJ, Cohn DH, Gibbs RA, Lee BH, Makitie O. WNT1 mutations in early-onset osteoporosis and osteogenesis imperfecta. N Engl J Med. 2013;368:1809–16.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  41. Shaheen R, Alazami AM, Alshammari MJ, Faqeih E, Alhashmi N, Mousa N, Alsinani A, Ansari S, Alzahrani F, Al-Owain M, Alzayed ZS, Alkuraya FS. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J Med Genet. 2012;49:630–5.

    Article  CAS  PubMed  Google Scholar 

  42. Symoens S, Malfait F, D’Hondt S, Callewaert B, Dheedene A, Steyaert W, Bachinger HP, De Paepe A, Kayserili H, Coucke PJ. Deficiency for the ER-stress transducer OASIS causes severe recessive osteogenesis imperfecta in humans. Orphanet J Rare Dis. 2013;8:154.

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgements

The authors are very grateful to Prof. Dr. Peter Fratzl (Max- Planck Institute of Colloids and Interfaces, Golm, Germany) for the long-standing cooperation and the helpful discussion during the preparation of this manuscript. The work at the Ludwig Boltzmann Institute of Osteology was supported by the AUVA (Austrian Social Insurance for Occupational Risk) and the WGKK (Social Health Insurance Vienna).

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All authors state that they have no conflicts of interest.

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Authors and Affiliations

  1. Ludwig Boltzmann Institute of Osteology, Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Med. Dept. Hanusch Hospital, Heinrich Collin Str. 30, 1140, Vienna, Austria

    Nadja Fratzl-Zelman PhD,  Barbara M. Misof PhD,  Paul Roschger PhD &  Klaus Klaushofer MD

  2. Ludwig Boltzmann Institute of Osteology, Trauma Center Meidling, Kundratstr. 37, A-1120, Vienna, Austria

    Nadja Fratzl-Zelman PhD

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  1. Nadja Fratzl-Zelman PhD
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Correspondence to Nadja Fratzl-Zelman PhD.

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Fratzl-Zelman, N., Misof, B., Roschger, P. et al. Classification of osteogenesis imperfecta. Wien Med Wochenschr 165, 264–270 (2015). https://doi.org/10.1007/s10354-015-0368-3

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