Fig. 4. The natural history of telomere biology disorders.

Each disorder has its own spectrum of clinical features. Hoyeraal–Hreidarsson Syndrome and Revesz Syndrome present early in childhood and are considered more severe subtypes of dyskeratosis congenita. Dyskeratosis congenita presents commonly in childhood but may manifest at any age. Patients classically present with the mucocutaneous triad of abnormal skin pigmentation, nail dyskeratosis and leukoplakia, and bone marrow failure is the most common cause of death. Idiopathic pulmonary fibrosis is the most common presentation and typically presents after the age of 60. A constellation of premature greying, bone marrow failure, pulmonary fibrosis and cryptogenic liver cirrhosis is suggestive of telomere biology disorders, but due to incomplete penetrance and various inheritance patterns of germline mutations, not all features may be present. The disease demonstrates anticipation with earlier and more severe manifestations down the generations. Across all phenotypes and ages, patients are at an increased risk of cancers.