Skip to main content
SpringerLink
Log in

Cushing proximal symphalangism and the NOG and GDF5 genes

  • Historical Perspective
  • Published:
Pediatric Radiology Aims and scope Submit manuscript

Abstract

Proximal symphalangism (SYM1) is an autosomal-dominant developmental disorder of joint fusion. This disorder is best known from famous historical descriptions of two large kindred: Cushing’s description in 1916 of the “straight-fingered” Brown family of Virginia and Drinkwater’s description in 1917 of the British Talbot family of noble blood, descended from the English war hero John Talbot, the first Earl of Shrewsbury (1388–1453). Recent genetic studies link this phenotype to expression of abnormal genes at future joint sites: too little expression of NOG, a growth antagonist, or overexpression of GDF5, a growth agonist, results in cartilage overgrowth and bony fusion. This review unites in depth the first historical accounts of SYM1 with a clinical description and reviews the current understanding of the molecular mechanism underlying what is likely the oldest dominant trait ever studied.

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
Fig. 8
Fig. 9

Similar content being viewed by others

References

  1. Cushing H (1916) Hereditary anchylosis of the proximal phalangeal joints (symphalangism). Genetics 1:90–106

    PubMed  CAS  Google Scholar 

  2. Strasburger AK, Hawkins MR, Eldridge R et al (1965) Symphalangism: genetics and clinical aspects. Bull Johns Hopkins Hosp 117:108–127

    Google Scholar 

  3. Drinkwater H (1917) Phalangeal anarthrosis (synostosis, ankylosis) transmitted through fourteen generations. Proc R Soc Med (Sect Pathol) 10:60–68

    Google Scholar 

  4. Elkington SG, Huntsman RG (1967) The Talbot fingers: a study in symphalangism. Br Med J 1:407–411

    Article  PubMed  CAS  Google Scholar 

  5. Geelhoed GW, Neel JV, Davidson RT (1969) Symphalangism and tarsal coalitions: a hereditary syndrome. J Bone Joint Surg Br 51B:278–289

    Google Scholar 

  6. Maroteaux P, Bouvet JP, Briard ML (1972) La maladie des synostoses multiples. Nouv Presse Med 1:3041–3047

    PubMed  CAS  Google Scholar 

  7. Brunet LJ, McMahon JA, McMahon AP et al (1998) Noggin, cartilage morphogenesis and joint formation in the mammalian skeleton. Science 280:1455–1457

    Article  PubMed  CAS  Google Scholar 

  8. Gong Y, Krakow D, Marcelino J et al (1999) Heterozygous mutations in the gene encoding noggin affect human joint morphogenesis. Nat Genet 21:302–304

    Article  PubMed  CAS  Google Scholar 

  9. d’Escouchy M (1863) Chronique de Mathieu d’Escouchy, vol 2 (edited by G du Fresne de Beaucourt). Mme Ve J. Renouard, Paris, p 39

  10. Seemann P, Schwappacher R, Kjaer KW et al (2005) Activating and deactivating mutations in the receptor interaction site of GDF5 cause symphalangism or bradydactyly type A2. J Clin Invest 115:2373–2381

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Physicians and Surgeons, Columbia University, New York, NY, USA

    Sara K. Plett

  2. Department of Radiology, Columbia Presbyterian Medical Center, New York, NY, USA

    Walter E. Berdon & Rahmi Oklu

  3. Division of Pediatric Surgery, Department of Surgery, Morgan Stanley Children’s Hospital of New York-Presbyterian, 3959 Broadway, CHN 216B, New York, NY, 10032, USA

    Robert A. Cowles

  4. Department of Radiology, Arnold Palmer Hospital for Children, Orlando, FL, USA

    John B. Campbell

Authors
  1. Sara K. Plett
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Walter E. Berdon
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Robert A. Cowles
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Rahmi Oklu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. John B. Campbell
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Robert A. Cowles.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Plett, S.K., Berdon, W.E., Cowles, R.A. et al. Cushing proximal symphalangism and the NOG and GDF5 genes. Pediatr Radiol 38, 209–215 (2008). https://doi.org/10.1007/s00247-007-0675-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00247-007-0675-y

Keywords

Search

Navigation