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Short Telomere Syndrome

Telomeres are hexanucleotide tandem repeats present at the ends of chromosomes which protect chromosomes from gradual degradation during cell division and aging. Once telomeres become critically shortened, the ends of chromosomes are exposed, which triggers the DNA damage response, p53 activation and apoptosis. For this reason, telomeres are referred to as molecular clocks.

Shortened telomere syndromes are clinically defined by premature loss of progenitor stem cells and reduced regenerative capacity of cells and organs. Organs with high cell turnover, such as bone marrow, liver, lungs and immune system are commonly affected. Clinical clues to a short telomere syndrome include premature graying of hair, cytopenias, hypogammaglobulinemia, cryptogenic cirrhosis and idiopathic pulmonary fibrosis.

Shortened telomere lengths are now believed to play an important role in a number of multisystem disorders including:

  • Bone marrow failure SSTs
    • Dyskeratosis congenita
    • Hoyeraal-Hreidarsson syndrome
    • Reverz syndrome
    • Cerebroretinal microangiopathy with calcifications and cysts
    • Aplastic anemia
    • Fanconi anemia
  • Pulmonary STSs
    • Idiopathic pulmonary fibrosis
    • Familial lung fibrosis
    • Fibrotic idiopathic interstitial pneumonia
  • Gastrointestinal STSs
    • Cryptogenic cirrhosis
    • Nodular regenerative hyperplasia

Flow cytometry with FISH is the preferred method to test for short telomere syndromes. Flow cytometry-FISH uses a fluorescent probe that binds to telomeres and allows flow cytometry-based assessment of telomere fluorescence in granulocytes and lymphocytes. The flow-FISH report should provide telomere length relative to age since telomeres normally shorten with aging. A patient is considered high risk if telomere length is <10% of normal. PCR based techniques are not recommended to determine telomere length because of their high variability. Testing currently costs about $1200 and is not covered by insurance.  


Mangaonkar AA and Patnaik MM, Short Telomere Syndromes in Clinical Practice: Bridging Bench and Bedside. Mayo Clin Proc 2018;93:904-16.

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