Dyskeratosis Congenita, Telomere Biology Disorders and the role of telomere length testing

Find out more about Dyskeratosis Congenita and Telomere Biology Disorders; what causes them, why the symptoms can vary and the importance of an accurate diagnosis.

What is Dyskeratosis Congenita?

Dyskeratosis Congenita (DC) is an inherited bone marrow failure syndrome that develops as a result of defective telomere maintenance. DC is therefore classed as a telomere biology disorder (TBD). TBDs are considered rare, and whilst their exact prevalence is not known, it is estimated that one in every million people have DC.

What are the symptoms?

DC can affect every organ system, resulting in a wide range of symptoms, however, the classic triad of symptoms includes abnormal skin coloration (lace pattern), nail dystrophy and white patches in the mouth (oral leukoplakia). In patients with this classic form of DC, the symptoms usually appear in childhood and bone marrow failure can follow in early adulthood.

However, there are also individuals who have a mild form, atypical DC, who may remain asymptomatic well into their adult lives and only present with related features (for example pulmonary fibrosis or bone marrow failure) in later life. It is even possible for an individual to carry a TBD mutation but never develop symptoms, although their children or grandchildren may do so.

Why is an accurate diagnosis so important?

Diagnosis of TBDs can be challenging, and there are a range of important factors that should be considered:

• The wide range of symptoms and varied presentation makes a diagnosis based on the clinical picture alone difficult
• The cost and time required for genetic testing, combined with the knowledge that a significant proportion of patients with TBDs do not have a known genetic mutation, highlights the need for another diagnostic option
• The increased incidence of lung fibrosis and cancer in individuals with TBDs means a conclusive diagnosis is vital to allow patient and physician awareness, prevention and regular monitoring
• The heritable nature of TBDs requires that patients have a thorough understanding of what this means for them, genetic counseling and guidance may be recommended to support with this

Patients with TBDs have very short telomeres for their age, as a result of deficient telomere maintenance. The development of telomere length testing, as well as increased knowledge around TBD-related genetic mutations, has vastly improved the diagnosis and helped to guide treatment of the conditions in clinical practice.

What guidelines are in place?

Clinical guidelines for the diagnosis and management of DC and TBDs have been developed and are freely available: Dyskeratosis Congenita and Telomere Biology Disorders: Diagnosis and Management Guidelines. These guidelines, authored by a group of TBD clinical experts and researchers, edited by Sharon A. Savage, MD and Elizabeth F. Cook, MD, were published by Team Telomere (previously Dyskeratosis Congenita Outreach Inc.).

How can you order a telomere length test?

RepeatDx is the leading laboratory offering comprehensive telomere length testing, providing results across 6 cell types (lymphocytes, granulocytes, memory and naïve T-cells, B-cells and NK cells). This level of testing supports the clinical diagnosis of TBDs – for example, a result of Low (L) or Very Low (VL) is required in four out of six cell groups to diagnose DC.

Order a telomere length analysis here.

Sources

Alter, B. et al. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood. 110, no. 5 (2007): 1439-1447. doi:10.1182/blood-2007-02-075598.

Ballew, B. & Savage, S. Updates on the biology and management of dyskeratosis congenita and related telomere biology disorders. Expert Review of Hematology. 2013. 6:3, 327-337. doi: 10.1586/ehm.13.23.

Nelson, N. & Bertuch, A. Dyskeratosis congenita as a disorder of telomere maintenance. Mutation research. 2011. 730(1-2), 43–51. doi:10.1016/j.mrfmmm.2011.06.008.

NIH: Genetics Home Reference. Dyskeratosis Congenita. 2019. Accessed at: https://ghr.nlm.nih.gov/condition/dyskeratosis-congenita#statistics

Savage, S. & Alter, B. Dyskeratosis congenita. Hematology/oncology clinics of North America. 2009. 23(2), 215–231. doi:10.1016/j.hoc.2009.01.003.

Savage, S & Bertuch, A. The genetics and clinical manifestations of telomere biology disorders. Genetics in Medicine. 2010.12(12):753–764. doi:10.1097/GIM.0b013e3181f415b5.

Savage, S. & Cook, E. Dyskeratosis Congenita and Telomere Biology Disorders: Diagnosis and Management Guidelines. (First ed.) 2015. Accessed at: https://teamtelomere.org/wp-content/uploads/2018/07/DC-TBD-Diagnosis-And-Management-Guidelines.pdf

Vulliamy, T. et al. Mutations in dyskeratosis congenita: their impact on telomere length and the diversity of clinical presentation. Blood. 2006. 107 (7) 2680-2685. doi: 10.1182/blood-2005-07-2622.