February 21, 2025
By: Sameep Sehgal, MBBS, FCCP; Brian Southern, MD; and Priya Balakrishnan, MD, FCCP
Diffuse Lung Disease and Lung Transplant Network
INFOGRAPHIC ON SHORT TELOMERE SYNDROME »
What are telomeres?
Our genetic information is stored in chromosomes, which are constantly dividing throughout our life. The ends of chromosomes have special structures called “telomeres,” which help protect the chromosomes from damage as they divide. The length of telomeres is longest at birth and decreases as we age, eventually becoming very short and making those cells unable to further divide. This shortening of telomeres is considered a part of normal aging.1
What is short telomere syndrome?
Telomere lengths significantly shorter than age-adjusted normal length (less than the 10th percentile) are considered short. Terms like short telomere syndrome (STS) or telomere biology disorder may be used to describe telomere abnormalities.2
How does STS impact the lungs?
Idiopathic pulmonary fibrosis (IPF) is the most common lung disease seen in those with STS.3 In genetic studies, about 25% of patients with IPF had shortened telomeres. In those with familial IPF, about 40% of patients had STS. Pulmonary fibrosis is often diagnosed at a younger age in those with STS and could be associated with an atypical pattern of scarring in the lung.4 Patients most commonly experience respiratory symptoms like shortness of breath, cough, and fatigue. A CT scan of the chest, breathing tests, and sometimes a lung biopsy are required to establish a diagnosis and determine severity. People with STS are also at increased risk for other lung diseases, such as emphysema and respiratory infections, and they are more susceptible to smoking-related lung injury.5
Which organs can be affected by STS?
STS can manifest with symptoms in childhood or later in life. In childhood, patients may present with bone marrow disorders, skin abnormalities, or nail abnormalities.6 In adults, the most common presentations are lung disease (IPF), bone marrow disease (myelodysplasia or bone marrow cancers), liver disease (cirrhosis), and signs of early aging (early greying of hair, coronary artery disease, etc). Patients may have single or multiple organ system involvement.7
How do we test for STS?
The telomere length can be measured by DNA analysis (Flow-FISH analysis) of WBCs (lymphocytes and granulocytes) through a blood test. The telomere length is then compared with age-adjusted normal values and commonly reported in percentiles.2 Testing is available at limited laboratories across the country.
Does having STS impact the treatment of IPF?
The presence of STS does not have a direct impact on the treatment of IPF. The US Food and Drug Administration-approved medications to treat IPF (pirfenidone and nintedanib) can be used in patients with STS and appear to be safe and effective.8 In certain situations, immune suppression medications may be needed as a part of the treatment plan. The risk of side effects from these medications (bone marrow suppression) and infections is higher in STS, requiring close monitoring by clinicians. Immunosuppression medications have also been shown to be harmful in patients with IPF and short telomeres.9
Does STS impact lung transplant care and outcomes?
Lung transplant may be an option for patients with severe lung disease, including those with STS. There are limited data on the impact of STS on lung transplant outcomes; however, patients with STS have similar survival after transplant compared with other patients with IPF. There is an increased risk of certain infections (like cytomegalovirus infection), slower wound healing, and increased side effects of antirejection medications (like bone marrow suppression) in those with STS.10
How may STS affect family members?
STS is a condition that can be inherited and can exhibit genetic anticipation, meaning the disease may occur earlier and with more severe symptoms in each generation. Key clues to suspect short telomeres are early greying of hair (age <30 years), unexplained low blood cell counts, pulmonary fibrosis, or liver cirrhosis. Genetic counseling should be considered in family members of patients with STS.11
What is the treatment for STS?
There is no specific treatment for STS. Treatment is directed at the affected organ systems. In those with lung disease, antifibrotic medications, supplemental oxygen, or lung transplant may be considered. In those with bone marrow disease, blood transfusions, treatment for any malignancy with chemotherapy, or a bone marrow transplant may be needed. Liver disease can be managed with medications, or sometimes a liver transplant is considered.12
Which clinicians are involved in patient care for those diagnosed with STS?
Patients with STS often need a multidisciplinary team depending on the organ systems affected. Pulmonary physicians, hematologists, hepatologists, and medical geneticists are among medical specialists that may be involved to help patients with STS.
Resources for patients
The Team Telomere website has resources that may be helpful for your patients.
References
- Turner KJ, Vasu V, Griffin DK. Telomere biology and human phenotype. Cells 2019;8(1):73.
- Baerlocher GM, Vulto I, de Jong G, Lansdorp PM. Flow cytometry and FISH to measure the average length of telomeres (flow FISH). Nat Protoc. 2006;1(5):2365-2376.
- Hutchinson J, Fogarty A, Hubbard R, McKeever T. Global incidence and mortality of idiopathic pulmonary fibrosis: a systematic review. Eur Respir J. 2015;46(3):795-806.
- Newton CA, Batra K, Torrealba J, et al. Telomere-related lung fibrosis is diagnostically heterogeneous but uniformly progressive. Eur Respir J. 2016;48(6):1710-1720.
- Courtwright AM, El-Chemaly S. Telomeres in interstitial lung disease: the short and the long of it. Ann Am Thorac Soc. 2019;16(2):175-181.
- Zheng B, Fu J. Telomere dysfunction in some pediatric congenital and growth-related diseases. Front Pediatr. 2023;11:1133102.
- Niewisch MR, Beier F, Savage SA. Clinical manifestations of telomere biology disorders in adults. Hematology Am Soc Hematol Educ Program. 2023;2023(1):563-572.
- Justet A, Klay D, Porcher R, et al; OrphaLung Network. Safety and efficacy of pirfenidone and nintedanib in patients with idiopathic pulmonary fibrosis and carrying a telomere-related gene mutation. Eur Respir J. 2021;57(2):2003198.
- Newton CA, Zhang D, Oldham JM, et al. Telomere length and use of immunosuppressive medications in idiopathic pulmonary fibrosis. Am J Respir Crit Care Med. 2019;200(3):336-347.
- Silhan LL, Shah PD, Chambers DC, et al. Lung transplantation in telomerase mutation carriers with pulmonary fibrosis. Eur Respir J. 2014;44(1):178-187.
- Ongie L, Raj HA, Stevens KB. Genetic counseling and family screening recommendations in patients with telomere biology disorders. Curr Hematol Malig Rep. 2023;18(6):273-283.
- Mangaonkar AA, Patnaik MM. Short telomere syndromes in clinical practice: bridging bench and bedside. Mayo Clin Proc. 2018;93(7):904-916.