• Open Access

The gastrointestinal manifestations of telomere-mediated disease

Authors

  • Naudia L. Jonassaint,

    1. Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Nini Guo,

    1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Joseph A. Califano,

    1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Department of Otolaryngology-Head & Neck Surgery, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    3. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Elizabeth A. Montgomery,

    1. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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  • Mary Armanios

    Corresponding author
    1. Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    2. Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    3. McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
    • Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA
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Correspondence

Mary Armanios, MD, Department of Oncology, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, 1650 Orleans street, CRB 1 Room 186, Baltimore, MD 21287, USA. Tel.: +1 410 502 3817; fax: +1 410 502 6240; e-mail: marmani1@jhmi.edu

Summary

Defects in telomere maintenance genes cause pathological telomere shortening, and manifest in syndromes which have prominent phenotypes in tissues of high turnover: the skin and bone marrow. Because the gastrointestinal (GI) epithelium is highly proliferative, we sought to determine whether telomere syndromes cause GI disease, and to define its prevalence, spectrum, and natural history. We queried subjects in the Johns Hopkins Telomere Syndrome Registry for evidence of luminal GI disease. In sixteen percent of Registry subjects (6 of 38), there was a history of significant GI pathology, and 43 additional cases were identified in the literature. Esophageal stenosis, enteropathy, and enterocolitis were the recurrent findings. In the intestinal mucosa, there was striking villous atrophy, extensive apoptosis, and anaphase bridging pointing to regenerative defects in the epithelial compartment. GI disease was often the first and most severe manifestation of telomere disease in young children. These findings indicate that telomere dysfunction disrupts the epithelial integrity in the human GI tract manifesting in recognizable disease processes. A high index of suspicion should facilitate diagnosis and management.

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