Clinical Correlates and Treatment Outcomes for Patients With Short Telomere Syndromes

Abhishek A. Mangaonkar, Alejandro Ferrer, Filippo Pinto e Vairo, Margot A. Cousin, Ryan J. Kuisle, Eric W. Klee, Cassie C. Kennedy, Steve G. Peters, J. P. Scott, James P. Utz, Misbah Baqir, Hiroshi Sekiguchi, Shakila P. Khan, Vilmarie Rodriguez, Douglas A. Simonetto, Patrick S. Kamath, Roshini S. Abraham, Mark E. Wylam, Mrinal M. Patnaik

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Short telomere syndromes (STSs) are accelerated aging syndromes with multisystemic manifestations that present complex management challenges. In this article, we discuss a single-institution experience in diagnosing and managing patients with inherited STSs. In total, we identified 17 patients with short telomeres, defined by flow-fluorescence in-situ hybridization telomere lengths of less than first centile in granulocytes/lymphocytes OR the presence of a characteristic germline pathogenic variant in the context of a highly suggestive clinical phenotype. Genetic variations in the telomere complex were identified in 6 (35%) patients, with 4 being known pathogenic variants involving TERT (n=2), TERC (n=1), and DKC1 (n=1) genes, while 2 were variants of uncertain significance in TERT and RTEL1 genes. Idiopathic interstitial pneumonia (IIP) (n=12 [71%]), unexplained cytopenias (n=5 [29%]), and cirrhosis (n=2 [12%]) were most frequent clinical phenotypes at diagnosis. At median follow-up of 48 (range, 0-316) months, Kaplan-Meier estimate of overall survival, median (95% CI), was 182 (113, not reached) months. Treatment modalities included lung transplantation for IIP (n=5 [29%]), with 3 patients developing signs of acute cellular rejection (2, grade A2; 1, grade A1); danazol therapy for cytopenias (n=4 [24%]), with only 1 out of 4 patients showing a partial hematologic response; and allogeneic hematopoietic stem cell transplant for progressive bone marrow failure (n=2), with 1 patient dying from transplant-related complications. In summary, patients with STSs present with diverse clinical manifestations and require a multidisciplinary approach to management, with organ-specific transplantation capable of providing clinical benefit.

Original languageEnglish (US)
Pages (from-to)834-839
Number of pages6
JournalMayo Clinic proceedings
Issue number7
StatePublished - Jul 2018

ASJC Scopus subject areas

  • General Medicine


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