What Are Telomeres?
The body’s genetic information is carried by your DNA, packaged into entities known as chromosomes. The ends of each chromosome are capped by structures called telomeres that function to protect chromosome ends during cell division. The cells of younger people have longer telomeres, but as people age, their telomeres become shorter. When its telomeres become too short, a cell may stop dividing as a way to protect itself from genetic damage. Shorter telomeres can adversely affect health and lifespan.
Research has revealed that genetic mutations can affect telomere length. In a group of conditions, known as Telomere Biology Disorders (or TBD), patients have premature or faster shortening of telomeres due to genetic mutations, causing impaired function of organs over time. The systems most affected in patients with TBD include bone marrow, blood, and skin, as well as the lungs and liver. Telomere defects also increase sensitivity to environmental and lifestyle factors such as cigarette smoking and alcohol consumption.
Telomere Biology Disorders (TBD)
People with TBD are born with or develop abnormally short telomeres. In some cases, severe telomere shortening is apparent during childhood, appearing as bone marrow failure, abnormal nails, and mouth and skin changes. The most widely recognized form of telomere biology disorder is known as dyskeratosis congenita (DC).
TBD can also manifest later in life. Adults can develop bone marrow failure, myelodysplastic syndrome, interstitial lung disease (ILD), and liver failure (cirrhosis). Adults with TBD are prone to skin and other cancers, including leukemia and head and neck tumors. Other effects include early hardening of the arteries, kidney dysfunction, liver and esophageal disease, joint disease, dental conditions, and even complications of pregnancy. These diseases may manifest appear, progress, and respond to treatment differently in patients with TBD.
Diagnosis
Patients with TBD can show symptoms in different ways, such as abnormal fingernails and toenails, white patches in the mouth, and atypical skin pigmentation (light and dark spots, or a lacy pattern). Others may not have these symptoms and may show bone marrow failure or low blood counts, or with lung fibrosis instead. Your doctors will use telomere length testing to determine a diagnosis of a telomere biology disorder.
Telomere Biology Disorders: The Penn Medicine Advantage
To ensure the best care and management of TBD, medical guidelines stress the importance of seeking treatment at specialized centers. Many of these programs, like Penn Medicine, are affiliated with medical schools and children’s hospitals. These institutions have a team of specialists with expertise in screening, diagnosing, and effectively treating the diverse manifestations of TBD.
At Penn Medicine, we provide comprehensive care and support for individuals affected by TBD. Our team of experienced clinicians and researchers are committed to delivering the highest quality of care, tailored to the unique needs of each patient. Through ongoing research collaboration, we strive to advance our understanding of TBD and improve the lives of those impacted by these disorders.
Multidisciplinary Care
Hematology
Anemia, low platelet count, and immune system dysfunction are among the most common symptoms associated with TBD. Patients with TBD face an increased risk of developing blood-related cancers, such as myelodysplastic syndrome and acute leukemia. These conditions require close monitoring and specialized management. Regular blood count and marrow screening are necessary to detect changes promptly. Long-term hematology care ensures comprehensive management while optimizing health and quality of life. For some patients, bone marrow failure or progression to blood cancers may require more intensive interventions. Bone marrow transplantation may be recommended in such cases, providing an avenue for effective treatment.
Interstitial Lung Disease
Some patients with TBD first seek medical attention when they develop interstitial lung disease (ILD), a build up of abnormal scar tissue in the lungs that causes difficulty breathing. Shortened telomere length in ILD was originally described in patients with a family history of interstitial pulmonary fibrosis (IPF), and up to a third of patients with a family history of IPF have shortened telomeres or carry a telomere-related mutation. Genetic research has also identified a variety of common, rare, and ultra-rare genetic variants in TBD-associated IPF and other forms of ILD.
The care of individuals with ILD due to TBD requires additional expertise because these patients may be at higher risk for toxicity from immunosuppressive therapies, as well as more rapid disease progression. Early referral to a center specializing in TBD (particularly those associated with transplant centers) is recommended.
Lung Transplantation
Between 15 to 20 percent of patients with IPF referred for lung transplant evaluation have TBD. For these patients, and those with ILD and TBD whose disease progresses despite standard therapies, lung transplantation is the most aggressive treatment. While TBD do not necessarily prohibit lung transplantation, specialized expertise is necessary to assess patients during the evaluation process. In addition, recipients with TBD are prone to more complications outside of the lungs and require multidisciplinary care.
Hepatology
Although less common than bone marrow and lung disease, TBD can also result in liver damage over time. Different TBD mutations may increase the risk of liver involvement and some patients with TBD can develop liver fibrosis or even cirrhosis (liver failure). Patients with TBD are also at risk for a rare liver condition called non-cirrhotic portal hypertension, which can be associated with life-threatening bleeding from abnormal blood vessels (varices) in the stomach and throat. In some cases, patients may require transplantation to manage their liver failure. TBD guidelines recommend routine blood tests to screen for liver involvement and, for patients with known liver disease, close monitoring for the development of cirrhosis and liver cancers.
Oral Medicine
Patients with TBD may exhibit a range of oral lesions, including white patches known as leukoplakia, as well as dental abnormalities. Among these manifestations, oral leukoplakia is observed in as many as 80 percent of cases. Oral leukoplakia related to TBD carries an increased risk of becoming cancers, particularly head and neck squamous cell carcinoma. The lesion might initially appear as subtle whitening or soreness of the oral mucosa (lining inside the mouth). To ensure early cancer detection and timely intervention, twice a year screening visits to Oral Medicine are highly recommended.
Medical Genetics
At Penn Medicine, precise genomic medicine has contributed to diagnosing patients with genetic diseases that impact multiple organ systems such as TBD. Because TBD is hereditary — each generation may be affected earlier or more severely — genetic testing is helpful in the diagnosis and screening of patients and family members. Genetics counselors discuss risk assessment for other family members, family planning, telomere and detailed genetic mutation testing options and implications, and psychological and social concerns.
About the Penn Medicine TBD Treatment Team
At the Penn Telomere Biology Disorders program, we understand the unique challenges that TBD presents. Our dedicated team is here to guide you through every step of your journey, providing expert care tailored to your specific needs. Together, we'll work towards managing your condition, enhancing your well-being, and achieving the best possible outcomes.
For Patients Transitioning from CHOP
Penn Medicine doctors work closely with pediatric colleagues caring for patients with TBD at the Children’s Hospital of Philadelphia Comprehensive Bone Marrow Failure Center to ensure a safe and easy transition for patients with TBD who are diagnosed as children. We also assist families and adult relatives of pediatric patients with screening for genetically inherited telomere biology disorders and establishing comprehensive TBD care.
Research and Clinical Trials
The Bone Marrow Failure Patient Registry and Sample Repository is an Internal Review Board-approved patient registry at the University of Pennsylvania and the Children’s Hospital of Philadelphia. The patient registry has over 700 currently enrolled pediatric and adult patients with different forms of bone marrow failure, including patients with TBD disorders.
The Penn TBD maintains a close collaboration with researchers at the University of Pennsylvania and nationally regarding registries, clinical trials, and other research studies relevant to care of patients with TBD.
Appointment Preparation and Resources
Before Your Appointment
When making an appointment, you will speak with one of our administrative assistants, who will review your prior medical history and register you in the Penn system (if you are not already). They will ask you general questions about your medical history and any prior surgeries or interventions.
Please have your insurance information available and ready when making an appointment so we can ensure that any necessary pre-authorizations are obtained in advance. We also encourage you to sign up for our patient portal (MyPennMedicine) prior to your visit, which facilitates communication with your care team.
If you have your medical records, we ask that you send copies to the office to be placed in your records with us. These include prior bone marrow, lung, medical genetics, or liver testing. Relevant imaging (such as chest x-rays, chest CT scans, liver ultrasound, etc) will be helpful, as well, so please bring a disk with images to your appointment if in your possession. Obtaining prior records is essential for us to be as prepared as possible when we see you.
Your Appointment
Each specialist in TBD Program is located in a different office area on the Penn Campus. Our administrative assistants will provide instructions regarding the location of your clinic visit and answer any questions you might have about directions and parking.
At your visit, you will meet your TBD specialist, and may also meet other team members, as well as medical trainees. Our team will provide specific recommendations in their area of expertise and will facilitate referrals to other members of TBD program, as appropriate.
Additional Resources
Make an Appointment
Please call 800-789-7366 or make an appointment.