Genetics of Osteogenesis Imperfecta Questions & Answers

1. Marini JC, Dang Do AN, Feingold KR, et al. Osteogenesis Imperfecta. Endotext. 2020 Jul 26. [QxMD MEDLINE Link]. [Full Text].

2. Subramanian S, Viswanathan VK. Osteogenesis Imperfecta. StatPearls. 2021 Jan. [QxMD MEDLINE Link]. [Full Text].

3. Ralston SH, Gaston MS. Management of Osteogenesis Imperfecta. Front Endocrinol (Lausanne). 2019. 10:924. [QxMD MEDLINE Link]. [Full Text].

4. Sillence DO, Senn A, Danks DM. Genetic heterogeneity in osteogenesis imperfecta. J Med Genet. 1979 Apr. 16(2):101-16. [QxMD MEDLINE Link].

5. Warman ML, Cormier-Daire V, Hall C, Krakow D, Lachman R, LeMerrer M. Nosology and classification of genetic skeletal disorders: 2010 revision. Am J Med Genet A. 2011 May. 155A(5):943-68. [QxMD MEDLINE Link].

6. Shaker JL, Albert C, Fritz J, Harris G. Recent developments in osteogenesis imperfecta. F1000Res. 2015. 4 (F1000 Faculty Rev):681. [QxMD MEDLINE Link]. [Full Text].

7. Rauch F, Munns C, Land C, Glorieux FH. Pamidronate in Children and Adolescents with Osteogenesis Imperfecta: Effect of Treatment Discontinuation. J Clin Endocrinol Metab. 2006. 91:1268-74. [QxMD MEDLINE Link].

8. Otaify GA, Aglan MS, Ibrahim MM, Elnashar M, El Banna RA, Temtamy SA. Zoledronic acid in children with osteogenesis imperfecta and Bruck syndrome: a 2-year prospective observational study. Osteoporos Int. 2016 Jan. 27 (1):81-92. [QxMD MEDLINE Link].

9. Lindahl K, Langdahl B, Ljunggren O, Kindmark A. Treatment of osteogenesis imperfecta in adults. Eur J Endocrinol. 2014 Aug. 171 (2):R79-90. [QxMD MEDLINE Link].

10. Castillo H, Samson-Fang L,. Effects of bisphosphonates in children with osteogenesis imperfecta: an AACPDM systematic review. Dev Med Child Neurol. 2009 Jan. 51(1):17-29. [QxMD MEDLINE Link].

11. Esposito P, Plotkin H. Surgical treatment of osteogenesis imperfecta: current concepts. Curr Opin Pediatr. 2008 Feb. 20(1):52-7. [QxMD MEDLINE Link].

12. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014 Apr 8. [QxMD MEDLINE Link].

13. Forlino A, Marini JC. Osteogenesis imperfecta. Lancet. 2016 Apr 16. 387 (10028):1657-71. [QxMD MEDLINE Link].

14. Balasubramanian M Md, Sobey GJ FCDerm, Wagner BE BSc Hons, et al. Osteogenesis imperfecta: Ultrastructural and histological findings on examination of skin revealing novel insights into genotype-phenotype correlation. Ultrastruct Pathol. 2016 Feb 10. 1-6. [QxMD MEDLINE Link].

15. Glorieux FH, Rauch F, Plotkin H, Ward L, Travers R, Roughley P, et al. Type V osteogenesis imperfecta: a new form of brittle bone disease. J Bone Miner Res. 2000 Sep. 15(9):1650-8. [QxMD MEDLINE Link].

16. Cho TJ, Lee KE, Lee SK, Song SJ, Kim KJ, Jeon D, et al. A single recurrent mutation in the 5'-UTR of IFITM5 causes osteogenesis imperfecta type V. Am J Hum Genet. 2012 Aug 10. 91(2):343-8. [QxMD MEDLINE Link]. [Full Text].

17. Glorieux FH, Ward LM, Rauch F, Lalic L, Roughley PJ, Travers R. Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect. J Bone Miner Res. 2002 Jan. 17(1):30-8. [QxMD MEDLINE Link].

18. Becker J, Semler O, Gilissen C, Li Y, Bolz HJ, Giunta C, et al. Exome sequencing identifies truncating mutations in human SERPINF1 in autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2011 Mar 11. 88(3):362-71. [QxMD MEDLINE Link]. [Full Text].

19. Barnes AM, Chang W, Morello R, Cabral WA, Weis M, Eyre DR, et al. Deficiency of cartilage-associated protein in recessive lethal osteogenesis imperfecta. N Engl J Med. 2006 Dec 28. 355(26):2757-64. [QxMD MEDLINE Link].

20. Christiansen HE, Schwarze U, Pyott SM, AlSwaid A, Al Balwi M, Alrasheed S, et al. 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 Mar 12. 86(3):389-98. [QxMD MEDLINE Link]. [Full Text].

21. Alanay Y, Avaygan H, Camacho N, Utine GE, Boduroglu K, Aktas D, et al. Mutations in the gene encoding the RER protein FKBP65 cause autosomal-recessive osteogenesis imperfecta. Am J Hum Genet. 2010 Apr 9. 86(4):551-9. [QxMD MEDLINE Link]. [Full Text].

22. Kelley BP, Malfait F, Bonafe L, Baldridge D, Homan E, Symoens S, et al. Mutations in FKBP10 cause recessive osteogenesis imperfecta and Bruck syndrome. J Bone Miner Res. 2011 Mar. 26(3):666-72. [QxMD MEDLINE Link]. [Full Text].

23. Barnes AM, Cabral WA, Weis M, Makareeva E, Mertz EL, Leikin S, et al. 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 Nov. 33(11):1589-98. [QxMD MEDLINE Link]. [Full Text].

24. Lapunzina P, Aglan M, Temtamy S, Caparrós-Martín JA, Valencia M, Letón R, et al. Identification of a frameshift mutation in Osterix in a patient with recessive osteogenesis imperfecta. Am J Hum Genet. 2010 Jul 9. 87(1):110-4. [QxMD MEDLINE Link]. [Full Text].

25. Nakashima K, Zhou X, Kunkel G, Zhang Z, Deng JM, Behringer RR, et al. The novel zinc finger-containing transcription factor osterix is required for osteoblast differentiation and bone formation. Cell. 2002 Jan 11. 108(1):17-29. [QxMD MEDLINE Link].

26. Martínez-Glez V, Valencia M, Caparrós-Martín JA, Aglan M, Temtamy S, Tenorio J, et al. Identification of a mutation causing deficient BMP1/mTLD proteolytic activity in autosomal recessive osteogenesis imperfecta. Hum Mutat. 2012 Feb. 33(2):343-50. [QxMD MEDLINE Link]. [Full Text].

27. Asharani PV, Keupp K, Semler O, Wang W, Li Y, Thiele H, et al. Attenuated BMP1 function compromises osteogenesis, leading to bone fragility in humans and zebrafish. Am J Hum Genet. 2012 Apr 6. 90(4):661-74. [QxMD MEDLINE Link]. [Full Text].

28. Shaheen R, Alazami AM, Alshammari MJ, Faqeih E, Alhashmi N, Mousa N, et al. Study of autosomal recessive osteogenesis imperfecta in Arabia reveals a novel locus defined by TMEM38B mutation. J Med Genet. 2012 Oct. 49(10):630-5. [QxMD MEDLINE Link].

29. Volodarsky M, Markus B, Cohen I, Staretz-Chacham O, Flusser H, Landau D, et al. A deletion mutation in TMEM38B associated with autosomal recessive osteogenesis imperfecta. Hum Mutat. 2013 Apr. 34(4):582-6. [QxMD MEDLINE Link].

30. Keupp K, Beleggia F, Kayserili H, Barnes AM, Steiner M, Semler O, et al. Mutations in WNT1 cause different forms of bone fragility. Am J Hum Genet. 2013 Apr 4. 92(4):565-74. [QxMD MEDLINE Link]. [Full Text].

31. Pyott SM, Tran TT, Leistritz DF, Pepin MG, Mendelsohn NJ, Temme RT, et al. WNT1 mutations in families affected by moderately severe and progressive recessive osteogenesis imperfecta. Am J Hum Genet. 2013 Apr 4. 92(4):590-7. [QxMD MEDLINE Link]. [Full Text].

32. Symoens S, Malfait F, D'hondt S, et al. Deficiency for the ER-stress transducer OASIS causes severe recessive osteogenesis imperfecta in humans. Orphanet J Rare Dis. 2013 Sep 30. 8:154. [QxMD MEDLINE Link].

33. Mendoza-Londono R, Fahiminiya S, Majewski J, et al. Recessive osteogenesis imperfecta caused by missense mutations in SPARC. Am J Hum Genet. 2015 Jun 4. 96 (6):979-85. [QxMD MEDLINE Link].

34. Doyard M, Bacrot S, Huber C, et al. FAM46A mutations are responsible for autosomal recessive osteogenesis imperfecta. J Med Genet. 2018 Apr. 55 (4):278-84. [QxMD MEDLINE Link].

35. Lindert U, Cabral WA, Ausavarat S, et al. MBTPS2 mutations cause defective regulated intramembrane proteolysis in X-linked osteogenesis imperfecta. Nat Commun. 2016 Jul 6. 7:11920. [QxMD MEDLINE Link]. [Full Text].

36. Hsieh JC, Lee L, Zhang L, et al. Mesd encodes an LRP5/6 chaperone essential for specification of mouse embryonic polarity. Cell. 2003 Feb 7. 112 (3):355-67. [QxMD MEDLINE Link]. [Full Text].

37. Moosa S, Yamamoto GL, Garbes L, et al. Autosomal-Recessive Mutations in MESD Cause Osteogenesis Imperfecta. Am J Hum Genet. 2019 Oct 3. 105 (4):836-43. [QxMD MEDLINE Link]. [Full Text].

38. Hsu VW, Shah N, Klausner RD. A brefeldin A-like phenotype is induced by the overexpression of a human ERD-2-like protein, ELP-1. Cell. 1992 May 15. 69 (4):625-35. [QxMD MEDLINE Link].

39. van Dijk FS, Semler O, Etich J, et al. Interaction between KDELR2 and HSP47 as a Key Determinant in Osteogenesis Imperfecta Caused by Bi-allelic Variants in KDELR2. Am J Hum Genet. 2020 Nov 5. 107 (5):989-99. [QxMD MEDLINE Link]. [Full Text].

40. Efthymiou S, Herman I, Rahman F, et al. Two novel bi-allelic KDELR2 missense variants cause osteogenesis imperfecta with neurodevelopmental features. Am J Med Genet A. 2021 Jul. 185 (7):2241-9. [QxMD MEDLINE Link]. [Full Text].

41. Shaheen R, Al-Owain M, Faqeih E, Al-Hashmi N, Awaji A, Al-Zayed Z, et al. Mutations in FKBP10 cause both Bruck syndrome and isolated osteogenesis imperfecta in humans. Am J Med Genet A. 2011 Jun. 155A(6):1448-52. [QxMD MEDLINE Link].

42. Puig-Hervás MT, Temtamy S, Aglan M, Valencia M, Martínez-Glez V, Ballesta-Martínez MJ, et al. Mutations in PLOD2 cause autosomal-recessive connective tissue disorders within the Bruck syndrome--osteogenesis imperfecta phenotypic spectrum. Hum Mutat. 2012 Oct. 33(10):1444-9. [QxMD MEDLINE Link].

43. Bank RA, Robins SP, Wijmenga C, Breslau-Siderius LJ, Bardoel AF, van der Sluijs HA, et al. Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17. Proc Natl Acad Sci U S A. 1999 Feb 2. 96(3):1054-8. [QxMD MEDLINE Link]. [Full Text].

44. Rush ET, Li L, Goodwin JL, et al. Echocardiographic phenotype in osteogenesis imperfecta varies with disease severity. Heart. 2017 Mar. 103 (6):443-8. [QxMD MEDLINE Link].

45. Kuurila K, Kaitila I, Johansson R, Grénman R. Hearing loss in Finnish adults with osteogenesis imperfecta: a nationwide survey. Ann Otol Rhinol Laryngol. 2002 Oct. 111(10):939-46. [QxMD MEDLINE Link].

46. Darba J, Marsa A. Hospital incidence, management and direct cost of osteogenesis imperfecta in Spain: a retrospective database analysis. J Med Econ. 2020 Dec. 23 (12):1435-40. [QxMD MEDLINE Link]. [Full Text].

47. Santos F, McCall AA, Chien W, Merchant S. Otopathology in Osteogenesis Imperfecta. Otol Neurotol. 2012 Dec. 33(9):1562-6. [QxMD MEDLINE Link]. [Full Text].

48. Machol K, Hadley TD, Schmidt J, et al. Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study. Am J Med Genet A. 2020 Apr. 182 (4):697-704. [QxMD MEDLINE Link].

49. Jain M, Tam A, Shapiro JR, et al. Growth characteristics in individuals with osteogenesis imperfecta in North America: results from a multicenter study. Genet Med. 2018 Jul 4. [QxMD MEDLINE Link].

50. Pillion JP, Shapiro J. Audiological findings in osteogenesis imperfecta. J Am Acad Audiol. 2008 Sep. 19(8):595-601. [QxMD MEDLINE Link].

51. Basal S, Ozgok Y, Tahmaz L, Atim A, Zor M, Bilgic S, et al. Extraperitoneal laparoscopy-assisted percutaneous nephrolithotomy in a patient with osteogenesis imperfecta. Urol Res. 2011 Feb. 39(1):73-6. [QxMD MEDLINE Link].

52. Rauch F, Travers R, Parfitt AM, Glorieux FH. Static and dynamic bone hystomorphometry in children with osteogenesis imperfecta. Bone. 2000. 26:581-9. [QxMD MEDLINE Link].

53. Bargman R, Huang A, Boskey AL, Raggio C, Pleshko N. RANKL Inhibition Improves Bone Properties in a Mouse Model of Osteogenesis Imperfecta. Connect Tissue Res. 2010 Jan 6. [QxMD MEDLINE Link].

54. Semler O, Netzer C, Hoyer-Kuhn H, Becker J, Eysel P, Schoenau E. First use of the RANKL antibody denosumab in osteogenesis imperfecta type VI. J Musculoskelet Neuronal Interact. 2012 Sep. 12 (3):183-8. [QxMD MEDLINE Link].

55. Hoyer-Kuhn H, Netzer C, Koerber F, Schoenau E, Semler O. Two years' experience with denosumab for children with osteogenesis imperfecta type VI. Orphanet J Rare Dis. 2014 Sep 26. 9:145. [QxMD MEDLINE Link].

56. Janus GJ, Finidori G, Engelbert RH, Pouliquen M, Pruijs JE. Operative treatment of severe scoliosis in osteogenesis imperfecta: results of 20 patients after halo traction and posterior spondylodesis with instrumentation. Eur Spine J. 2000 Dec. 9(6):486-91. [QxMD MEDLINE Link]. [Full Text].

57. [Guideline] Mueller B, Engelbert R, Baratta-Ziska F, et al. Consensus statement on physical rehabilitation in children and adolescents with osteogenesis imperfecta. Orphanet J Rare Dis. 2018 Sep 10. 13 (1):158. [QxMD MEDLINE Link]. [Full Text].

58. Sasaki-Adams D, Kulkarni A, Rutka J, Dirks P, Taylor M, Drake JM. Neurosurgical implications of osteogenesis imperfecta in children. Report of 4 cases. J Neurosurg Pediatr. 2008 Mar. 1(3):229-36. [QxMD MEDLINE Link].

59. Paterson CR, Ogston SA, Henry RM. Life expectancy in osteogenesis imperfecta. BMJ. 1996 Feb 10. 312 (7027):351. [QxMD MEDLINE Link]. [Full Text].

60. McAllion SJ, Paterson CR. Causes of death in osteogenesis imperfecta. J Clin Pathol. 1996 Aug. 49 (8):627-30. [QxMD MEDLINE Link]. [Full Text].

61. Folkestad L, Hald JD, Canudas-Romo V, et al. Mortality and Causes of Death in Patients With Osteogenesis Imperfecta: A Register-Based Nationwide Cohort Study. J Bone Miner Res. 2016 Dec. 31 (12):2159-66. [QxMD MEDLINE Link]. [Full Text].

62. Folkestad L. Mortality and morbidity in patients with osteogenesis imperfecta in Denmark. Dan Med J. 2018 Apr. 65 (4):[QxMD MEDLINE Link].

Eric T Rush, MD, FAAP Professor of Pediatrics, University of Missouri-Kansas City School of Medicine; Clinical Geneticist, Children's Mercy Hospital of Kansas City

Eric T Rush, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American College of Physicians

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical, Biomarin Pharmaceuticals, ObsEva, Inozyme Pharma, Ascendis Pharma<br/>Serve(d) as a speaker or a member of a speakers bureau for: Alexion Pharmaceuticals, Ultragenyx Pharmaceutical, and Biomarin Pharmaceuticals<br/>Received research grant from: Alexion Pharmaceuticals, Ultragenyx Pharmaceuticals.

Horacio B Plotkin, MD, FAAP Chief Medical Officer, Retrophin, Inc; Adjunct Associate Professor of Pediatrics and Orthopedic Surgery, University of Nebraska College of Medicine

Horacio B Plotkin, MD, FAAP is a member of the following medical societies: American Academy of Pediatrics

Disclosure: Received salary from PPD, Inc for: PPD.

Luis O Rohena, MD, PhD, FAAP, FACMG Deputy Chief, Department of Pediatrics, Chief, Medical Genetics, San Antonio Military Medical Center; Associate Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Associate Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD, PhD, FAAP, FACMG is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Horatio Plotkin, MD, FAAP, to the development and writing of this article.

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and American Society of Human Genetics

Disclosure: Nothing to disclose.

Alexander A Cacciarelli, MD, FACR Consulting Staff, Department of Radiology, St Joseph's Hospital and Medical Center of Phoenix

Disclosure: Nothing to disclose.

Mandar A Pattekar, MD, MS Consulting Staff, Department of Radiology, Methodist Hospital

Disclosure: Nothing to disclose.

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

• Print this section
• Print the entire contents of
• Print the entire contents of article