Syndromes of telomere shortening

Annu Rev Genomics Hum Genet. 2009:10:45-61. doi: 10.1146/annurev-genom-082908-150046.


Telomeres and telomerase were initially discovered in pursuit of questions about how the ends of chromosomes are maintained. The implications of these discoveries to age-related disease have emerged in recent years with the recognition of a group of telomere-mediated syndromes. Telomere-mediated disease was initially identified in the context of dyskeratosis congenita, a rare syndrome of premature aging. More recently, mutations in telomerase components were identified in adults with idiopathic pulmonary fibrosis. These findings have revealed that the spectrum of telomere-mediated disease is broad and includes clinical presentations in both children and adults. We have previously proposed that these disorders be collectively considered as syndromes of telomere shortening. Here, the spectrum of these disorders and the unique telomere genetics that underlies them are reviewed. I also propose broader clinical criteria for defining telomere-mediated syndromes outside of dyskeratosis congenita, with the goal of facilitating their diagnosis and highlighting their pathophysiology.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dyskeratosis Congenita / genetics*
  • Dyskeratosis Congenita / physiopathology
  • Genetic Predisposition to Disease
  • Humans
  • Pulmonary Fibrosis / genetics*
  • Pulmonary Fibrosis / physiopathology
  • Syndrome
  • Telomerase / deficiency
  • Telomerase / genetics
  • Telomerase / metabolism
  • Telomere / chemistry
  • Telomere / genetics*
  • Telomere / metabolism*


  • Telomerase