TGF-β signalopathies as a paradigm for translational medicine

Eur J Med Genet. 2015 Dec;58(12):695-703. doi: 10.1016/j.ejmg.2015.10.010. Epub 2015 Oct 24.


This review focusses on impact of a better knowledge of pathogenic mechanisms of Marfan and related disorders on their treatment strategies. It was long believed that a structural impairment formed the basis of Marfan syndrome as deficiency in the structural extracellular matrix component, fibrillin-1 is the cause of Marfan syndrome. However, the study of Marfan mouse models has revealed the strong involvement of the transforming growth factor-β signalling pathway in the pathogenesis of Marfan. Similarly, this pathway was demonstrated to be key in the pathogenesis of Loeys-Dietz and Shprintzen-Goldberg syndrome. The elucidation of the underlying pathogenic mechanisms has led to new treatment strategies, targeting the overactive TGF-β pathway. Various clinical trials are currently investigating the potential new treatment options. A meta-analysis will contribute to a better understanding of the various trial results.

Keywords: Angiotensin receptor blocker; Beta blocker; Loeys-Dietz syndrome; Marfan syndrome; Shprintzen-Goldberg syndrome; Transforming growth factor beta.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Arachnodactyly / diagnosis
  • Arachnodactyly / genetics
  • Arachnodactyly / metabolism
  • Arachnodactyly / therapy
  • Craniosynostoses / diagnosis
  • Craniosynostoses / genetics
  • Craniosynostoses / metabolism
  • Craniosynostoses / therapy
  • Humans
  • Loeys-Dietz Syndrome / diagnosis
  • Loeys-Dietz Syndrome / genetics
  • Loeys-Dietz Syndrome / metabolism
  • Loeys-Dietz Syndrome / therapy
  • Marfan Syndrome / diagnosis
  • Marfan Syndrome / genetics
  • Marfan Syndrome / metabolism
  • Marfan Syndrome / therapy
  • Signal Transduction*
  • Transforming Growth Factor beta / metabolism*
  • Translational Research, Biomedical*


  • Transforming Growth Factor beta

Supplementary concepts

  • Shprintzen Golberg craniosynostosis