Skip to main content

Advertisement

SpringerLink
Log in

Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis

  • PAEDIATRIC RADIOLOGY
  • Published:
La radiologia medica Aims and scope Submit manuscript

Abstract

Objective

The purpose of the paper was to assess the morphometric parameters to improve the specificity of the ultrasound (US) signs for the early differential diagnosis between two lethal dysplasias, as thanatophoric dysplasia (TD) and osteogenesis imperfecta type 2 (OI-2).

Method

The diaphyseal length and the bowed shape of long bones associated with vertebral body dimension assessment were investigated in a group of 14 pregnancy terminations carried out in the time period 2007–2013. The definitive diagnosis was established after pregnancy termination by means of skeletal standardized X-rays, histopathology and gene analysis.

Results

TD and OI-2 long bones were significantly shorter than controls. No significant differences were observed between the two dysplasias. The bowing angle was higher in OI-2; a true angulation or eventually axial displacement was present only in the latter. Furthermore, they did not show any evidence of vertebral collapse. The thanatophoric dysplasia presented less bowed long bones, and never true angulation. The spine was steadily characterized by flattened anterior vertebral bodies.

Conclusion

Long bone shortening is not a sufficient and accurate sign for early sonographic differential diagnosis between TD and OI-2. Angled diaphysis, axial diaphyseal displacement and a conserved vertebral body height in the prenatal period support the diagnosis of osteogenesis imperfecta type 2, while moderately regular bowed diaphysis associated with platyspondyly that of thanatophoric dysplasia.

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
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Alanay Y, Krakow D, Rimoin DL et al (2007) Angulated femurs and the skeletal dysplasia: experience of the international skeletal dysplasia registry (1988–2006). Am J Genet A 143:1159–1168

    Article  Google Scholar 

  2. Schild RL, Hunt GH, Moore J et al (1996) Antenatal sonographic diagnosis of thanatophoric dysplasia: a report of three cases and a review of the literature with special emphasis on the differential diagnosis. Ultrasound Obstet Gynecol 8:62–67

    Article  CAS  PubMed  Google Scholar 

  3. Wilcox WR, Tavormina PL, Krakow D et al (1998) Molecular, radiologic, and histopathologic correlations in thanatophoric dysplasia. Am J Med Genet 78:274–281

    Article  CAS  PubMed  Google Scholar 

  4. Tonni G, Azzoni D, Ventura A et al (2010) Thanatophoric dysplasia type I associated with increased nuchal translucency in the first trimester: early prenatal diagnosis using combined ultrasonography and molecular biology. Fetal Pediatr Pathol 29:314–322

    Article  CAS  PubMed  Google Scholar 

  5. Chitty LS, Khalil A, Barrett AN et al (2013) Safe, accurate, prenatal diagnosis of thanatophoric dysplasia using ultrasound and free fetal DNA. Prenat Diagn 33:416–423

    Article  CAS  PubMed  Google Scholar 

  6. Teele RL (2006) A guide to the recognition of skeletal disorders in the fetus. Pediatr Radiol 36:473–484

    Article  PubMed  Google Scholar 

  7. Khalil A, Pajkrt E, Chitty LS (2011) Early prenatal diagnosis of skeletal anomalies. Prenat Diagn 31:115–124

    Article  PubMed  Google Scholar 

  8. Giancotti A, Castori M, Spagnuolo A et al (2011) Early ultrasound suspect of thanatophoric dysplasia followed by first trimester molecular diagnosis. Am J Med Genet A 155:1756–1758

    Article  Google Scholar 

  9. Iwata T, Chen L, Li C et al (2000) A neonatal lethal mutation in FGFR3 uncouples proliferation and differentiation of growth plate chondrocytes in embryos. Hum Mol Genet 9:1603–1613

    Article  CAS  PubMed  Google Scholar 

  10. Lievens PM, Liboi E (2003) The thanatophoric dysplasia type II mutation hampers complete maturation of fibroblast growth factor receptor 3 (FGFR3), which activates signal transducer and activator of transcription 1 (STAT1) from the endoplasmic reticulum. J Biol Chem 278:17344–17349

    Article  CAS  PubMed  Google Scholar 

  11. Martínez-Frías ML, de Frutos CA, Bermejo E et al (2010) ECEMC Working Group. Review of the recently defined molecular mechanisms underlying thanatophoric dysplasia and their potential therapeutic implications for achondroplasia. Am J Med Genet A 152:245–255

    Article  Google Scholar 

  12. Forlino A, Cabral WA, Barnes AM et al (2011) New perspectives on osteogenesis imperfecta. Nat Rev Endocrinol 7:540–557

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Van Dijk FS, Nesbitt IM, Nikkels PG et al (2009) CRTAP mutations in lethal and severe osteogenesis imperfecta: the importance of combining biochemical and molecular genetic analysis. Eur J Hum Genet 17:1560–1569

    Article  PubMed  PubMed Central  Google Scholar 

  14. Bellus GA, Spector EB, Speiser PW et al (2000) Distinct missense mutations of the FGFR3 lys650 codon modulate receptor kinase activation and the severity of the skeletal dysplasia phenotype. Am J Hum Genet 67:1411–1421

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Dighe M, Fligner C, Cheng E et al (2008) Fetal skeletal dysplasia: an approach to diagnosis with illustrative cases. Radiographics 28:1061–1077

    Article  PubMed  Google Scholar 

  16. Renna MD, Pisani P, Conversano F et al (2013) Sonographic markers for early diagnosis of fetal malformations. World J Radiol 5:356–371

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cassart M (2010) Suspected fetal skeletal malformations or bone diseases: how to explore. Pediatr Radiol 40:1046–1051

    Article  PubMed  Google Scholar 

  18. Parilla BV, Leeth EA, Kambich MP et al (2003) Antenatal detection of skeletal dysplasias. J Ultrasound Med 22:255–258

    Article  PubMed  Google Scholar 

  19. Pazzaglia UE, Donzelli CM, Izzi C et al (2014) Thanatophoric dysplasia. Correlation among bone X-ray morphometry, histopathology, and gene analysis. Skeletal Radiol 43:1205–1215

    Article  PubMed  Google Scholar 

  20. Tsai PY, Chang CH, Yu CH et al (2012) Three-dimensional ultrasound in the prenatal diagnosis of osteogenesis imperfecta. Taiwan J Obstet Gynecol 51:387–392

    Article  PubMed  Google Scholar 

  21. Rouse GA, Filly RA, Toomey F et al (1990) Short-limb skeletal dysplasias: evaluation of the fetal spine with sonography and radiography. Radiology 174:177–180

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pediatric Radiology, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, P.le Spedali Civili n. 1, 25100, Brescia, Italy

    Maria Pia Bondioni, Giuseppe Di Gaetano & Francesco Laffranchi

  2. Orthopaedic Clinic, Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy

    Ugo Ernesto Pazzaglia

  3. Prenatal Diagnosis Unit, Department of Obstretics and Gynecology, ASST Spedali Civili of Brescia, Brescia, Italy

    Claudia Izzi & Federico Prefumo

  4. Genetic Laboratory Galliera Hospital Genova, Genoa, Italy

    Maurizia Baldi

Authors
  1. Maria Pia Bondioni
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ugo Ernesto Pazzaglia
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Claudia Izzi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Giuseppe Di Gaetano
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Francesco Laffranchi
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Maurizia Baldi
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Federico Prefumo
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Pia Bondioni.

Ethics declarations

Conflict of interest

The authors declare no conflicts of interest.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

Funding

No funding was received for this research.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Bondioni, M.P., Pazzaglia, U.E., Izzi, C. et al. Comparative X-ray morphometry of prenatal osteogenesis imperfecta type 2 and thanatophoric dysplasia: a contribution to prenatal differential diagnosis. Radiol med 122, 880–891 (2017). https://doi.org/10.1007/s11547-017-0784-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11547-017-0784-0

Keywords

Search

Navigation