Historical Perspective

Pediatric Radiology

, Volume 38, Issue 2, pp 209-215

First online:

Cushing proximal symphalangism and the NOG and GDF5 genes

  • Sara K. PlettAffiliated withCollege of Physicians and Surgeons, Columbia University
  • , Walter E. BerdonAffiliated withDepartment of Radiology, Columbia Presbyterian Medical Center
  • , Robert A. CowlesAffiliated withDivision of Pediatric Surgery, Department of Surgery, Morgan Stanley Children’s Hospital of New York-Presbyterian Email author 
  • , Rahmi OkluAffiliated withDepartment of Radiology, Columbia Presbyterian Medical Center
  • , John B. CampbellAffiliated withDepartment of Radiology, Arnold Palmer Hospital for Children

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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.


Symphalangism Noggin and GDF5 Children