Abstract IA19: Dyskeratosis congenita and related syndromes

Abstract

Abstract Dyskeratosis Congenita (DC) is a heterogeneous multi-system syndrome exhibiting marked clinical and genetic heterogeneity. In its classical form it is characterized by mucocutaneous abnormalities (abnormal skin pigmentation, nail dystrophy, leucoplakia), bone marrow failure and a high predisposition to malignancy (hematological and non-hematological). Bone marrow failure is the principal cause of mortality and patients display features of premature aging (including early dental loss, premature greying and osteoporosis). Studies over the last 15 years have led to significant advances with ten DC genes (DKC1, TERC, TERT, NOP10, NHP2, TINF2, USB1, TCAB1, CTC1 and RTEL1) having been characterized. Nine of these are important in telomere maintenance. DC is therefore principally a disease of defective telomere maintenance and patients usually have very short/ and or abnormal telomeres. The genetic advances have also led to the unification of DC with a number of other disorders. This includes the severe multi-system disorders Hoyeraal-Hreidarsson and Revesz syndromes as well as a subset of patients with aplastic anemia, myelodysplasia, leukemia, liver disease and idiopathic pulmonary fibrosis. This wide spectrum of diseases ranging from classical DC to aplastic anemia can be regarded as disorders of defective telomere maintenance - “the telomereopathies”. These advances have increased our understanding of several human diseases (including genetic predisposition to subtypes of cancer) and highlighted the importance of telomere maintenance in human biology. They are also facilitating diagnosis (especially when presentation is atypical) and management. Correct early diagnosis is important as bone marrow failure associated with this group of disorders is unlikely to respond to immunosuppressive agents and is more likely to respond to anabolic steroids such as oxymetholone. For patients who are unresponsive to anabolic steroids allogeneic hematopoietic stem cell transplantation using fludarabine based low intensity protocols is producing encouraging results. Citation Format: Inderjeet Dokal. Dyskeratosis congenita and related syndromes. [abstract]. In: Proceedings of the AACR Special Conference: Cancer Susceptibility and Cancer Susceptibility Syndromes; Jan 29-Feb 1, 2014; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(23 Suppl):Abstract nr IA19. doi:10.1158/1538-7445.CANSUSC14-IA19