Cushing proximal symphalangism and the NOG and GDF5 genes

Pediatr Radiol. 2008 Feb;38(2):209-15. doi: 10.1007/s00247-007-0675-y. Epub 2007 Nov 10.

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.

Publication types

  • Historical Article

MeSH terms

  • Bone Morphogenetic Proteins / genetics
  • Carrier Proteins / genetics
  • Finger Joint / abnormalities*
  • Finger Joint / diagnostic imaging
  • Growth Differentiation Factor 5
  • History, 20th Century
  • Humans
  • Joint Diseases / diagnostic imaging
  • Joint Diseases / genetics
  • Joint Diseases / history*
  • Mutation
  • Phenotype
  • Radiography

Substances

  • Bone Morphogenetic Proteins
  • Carrier Proteins
  • GDF5 protein, human
  • Growth Differentiation Factor 5
  • noggin protein