Skip to main content

Advertisement

SpringerLink
Log in

Skeletal Dysplasias: What Every Bone Health Clinician Needs to Know

  • Pediatrics (L Ward and E Imel, Section Editors)
  • Published:
Current Osteoporosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

This review highlights how skeletal dysplasias are diagnosed and how our understanding of some of these conditions has now translated to treatment options.

Recent Findings

The use of multigene panels, using next-generation sequence technology, has improved our ability to quickly identify the genetic etiology, which can impact management. There are successes with the use of growth hormone in individuals with SHOX deficiencies, asfotase alfa in hypophosphatasia, and some promising data for c-type natriuretic peptide for those with achondroplasia.

Summary

One needs to consider that a patient with short stature has a skeletal dysplasia as options for management may be available.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: •Of importance ••Of major importance

  1. International nomenclature of constitutional diseases of bones. Ann Radiol (Paris). 1970;13:455–64.

  2. Bonafe L, Cormier-Daire V, Hall C, Lachman R, Mortier G, Mundlos S, et al. Nosology and classification of genetic skeletal disorders: 2015 revision. Am J Med Genet A. 2015;167A:2869–92. doi:10.1002/ajmg.a.37365.

  3. Gripp KW, Slavotinek AM, Hall JG, Allanson JE. Handbook of physical measurements, 3rd edition. Oxford: Oxford University Press; 2013.

    Book  Google Scholar 

  4. Watson SG, Calder AD, Offiah AC, Negus S. A review of imaging protocols for suspected skeletal dysplasia and a proposal for standardisation. Pediatr Radiol. 2015;45:1733–7. doi:10.1007/s00247-015-3381-1.

    Article  PubMed  Google Scholar 

  5. Rehm HL, Bale SJ, Bayrak-Toydemir P, Berg JS, Brown KK, Deignan JL, et al., Working Group of the American College of Medical Genetics and Genomics Laboratory Quality Assurance Commitee. ACMG clinical laboratory standards for next-generation sequencing. Genet Med. 2013;15:733–47. doi:10.1038/gim.2013.92.

  6. Sobacchi C, Frattini A, Guerrini MM, Abinun M, Pangrazio A, Susani L, et al. Osteoclast-poor human osteopetrosis due to mutations in the gene encoding RANKL. Nat Genet. 2007;39:960–2. doi:10.1038/ng2076.

  7. Trotter TL, Hall JG, American Academy of Pediatrics Committee on Genetics. Health supervision for children with achondroplasia. Pediatrics. 2005;116:771–83. doi:10.1542/peds.2005-1440.

    Article  PubMed  Google Scholar 

  8. Tunkel D, Alade Y, Kerbavaz R, Smith B, Rose-Hardison D, Hoover-Fong J. Hearing loss in skeletal dysplasia patients. Am J Med Genet A. 2012;158A:1551–5. doi:10.1002/ajmg.a.35373.

    Article  PubMed  Google Scholar 

  9. • Flechtner I, Lambot-Juhan K, Teissier R, Colmenares A, Baujat G, Beltrand J, et al. Unexpected high frequency of skeletal dysplasia in idiopathic short stature and small for gestational age patients. Eur J Endocrinol. 2014;170:677–84. doi:10.1530/EJE-13-0864. The authors demonstrate that in the population of short statured individuals, there is a higher than expected frequency of skeletal dysplasias.

  10. Benabbad I, Rosilio M, Child CJ, Carel JC, Ross JL, Deal CL, et al. Safety outcomes and near-adult height gain of growth hormone-treated children with SHOX deficiency: data from an observational study and a clinical trial. Horm Res Paediatr. 2017;87:42–50. doi:10.1159/000452973.

  11. Hirschfeldova K, Florianova M, Kebrdlova V, Urbanova M, Stekrova J. Detection of SHOX gene aberrations in routine diagnostic practice and evaluation of phenotype scoring form effectiveness. J Hum Genet. 2017;62:253–7. doi:10.1038/jhg.2016.117.

    Article  CAS  PubMed  Google Scholar 

  12. Dwan K, Phillipi CA, Steiner RD, Basel D. Bisphosphonate therapy for osteogenesis imperfecta. Cochrane Database Syst Rev. 2016;10 doi:10.1002/14651858.CD005088.

  13. Chusho H, Tamura N, Ogawa Y, Yasoda A, Suda M, Miyazawa T, et al. Dwarfism and early death in mice lacking C-type natriuretic peptide. Proc Natl Acad Sci U S A. 2001;98:4016–21. doi:10.1073/pnas.071389098.

  14. Tsuji T, Kunieda T. A loss-of-function mutation in natriuretic peptide receptor 2 (Npr2) gene is responsible for disproportionate dwarfism in cn/cn mouse. J Biol Chem. 2005;280:14288–92. doi:10.1074/jbc.C500024200.

    Article  CAS  PubMed  Google Scholar 

  15. Yasoda A, Komatsu Y, Chusho H, Miyazawa T, Ozasa A, Miura M, et al. Overexpression of CNP in chondrocytes rescues achondroplasia through a MAPK-dependent pathway. Nat Med. 2004;10:80–6. doi:10.1038/nm971.

  16. •• Lorget F, Kaci N, Peng J, Benoist-Lasselin C, Mugniery E, Oppeneer T, et al. Evaluation of the therapeutic potential of a CNP analog in a Fgfr3 mouse model recapitulating achondroplasia. Am J Hum Genet. 2012;91:1108–14. doi:10.1016/j.ajhg.2012.10.014. The authors provide evidence that an analog of CNP has the potential to improve bone growth in those with achondroplasia.

  17. Wendt DJ, Dvorak-Ewell M, Bullens S, Lorget F, Bell SM, Peng J, et al. Neutral endopeptidase-resistant C-type natriuretic peptide variant represents a new therapeutic approach for treatment of fibroblast growth factor receptor 3-related dwarfism. J Pharmacol Exp Ther. 2015;353:132–49. doi:10.1124/jpet.114.218560.

  18. Whyte MP. Hypophosphatasia—aetiology, nosology, pathogenesis, diagnosis and treatment. Nat Rev Endocrinol. 2016;12:233–46. doi:10.1038/nrendo.2016.14.

    Article  CAS  PubMed  Google Scholar 

  19. •• Whyte MP, Madson KL, Phillips D, Reeves AL, McAlister WH, Yakimoski A, et al. Asfotase alfa therapy for children with hypophosphatasia. JCI Insight. 2016;1 doi:10.1172/jci.insight.85971. The authors demonstrate that asfotase alfa has the ability to improve the lives of children with hypophosphatasia.

  20. Whyte MP, Rockman-Greenberg C, Ozono K, Riese R, Moseley S, Melian A, et al. Asfotase alfa treatment improves survival for perinatal and infantile hypophosphatasia. J Clin Endocrinol Metab. 2016;101:334–42. doi:10.1210/jc.2015-3462.

  21. Tomatsu S, Sawamoto K, Shimada T, Bober MB, Kubaski F, Yasuda E, et al. Enzyme replacement therapy for treating mucopolysaccharidosis type IVA (Morquio A syndrome): effect and limitations. Expert Opin Orphan Drugs. 2015;3:1279–90. doi:10.1517/21678707.2015.1086640.

Download references

Acknowledgements

I want to thank L.W. and E.I. for inviting me to write this article. I also want to express my appreciation to all the clinicians and families I have learned from over the years.

Author information

Authors and Affiliations

  1. Provinical Medical Genetics Program, BC Women’s Hospital and Health Centre, University of British Columbia, 4500 Oak Street, Vancouver, BC, V6H 3N1, Canada

    Sarah M. Nikkel

Authors
  1. Sarah M. Nikkel
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Sarah M. Nikkel.

Ethics declarations

Conflict of Interest

Sarah Nikkel declares no conflicts of interest.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by the author.

Additional information

This article is part of the Topical Collection on Pediatrics

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Nikkel, S.M. Skeletal Dysplasias: What Every Bone Health Clinician Needs to Know. Curr Osteoporos Rep 15, 419–424 (2017). https://doi.org/10.1007/s11914-017-0392-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11914-017-0392-x

Keywords

Search

Navigation