Dyskeratosis congenita

Hematology Am Soc Hematol Educ Program. 2011:2011:480-6. doi: 10.1182/asheducation-2011.1.480.

Abstract

Dyskeratosis congenita (DC) is a multisystem inherited syndrome exhibiting marked clinical and genetic heterogeneity. In its classic form, it is characterized by mucocutaneous abnormalities, BM failure, and a predisposition to cancer. BM failure is the principal cause of premature mortality. Studies over the last 15 years have led to significant advances, with 8 DC genes (DKC1, TERC, TERT, NOP10, NHP2, TIN2, C16orf57, and TCAB1) having been characterized. Seven of these are important in telomere maintenance either because they encode components of the telomerase enzyme complex (DKC1, TERC, TERT, NOP10, NHP2, and TCAB1) or the shelterin complex (TINF2). DC is therefore principally a disease of defective telomere maintenance and patients usually have very short telomeres. The genetic advances have led to the unification of DC with several other disorders, including the severe multisystem disorders Hoyeraal-Hreidarsson and Revesz syndromes, as well as a subset of patients with aplastic anemia, myelodysplasia, leukemia, and idiopathic pulmonary fibrosis. This wide spectrum of diseases ranging from classic DC to aplastic anemia can be regarded as disorders of defective telomere maintenance-"the telomereopathies." These advances have increased our understanding of normal hematopoiesis and highlighted the important role of telomerase and telomeres in human biology. They are also facilitating the diagnosis (especially when presentation is atypical) and management of DC.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Dyskeratosis Congenita / complications
  • Dyskeratosis Congenita / pathology*
  • Dyskeratosis Congenita / physiopathology
  • Dyskeratosis Congenita / therapy
  • Fetal Growth Retardation
  • Genes, Dominant / genetics
  • Genetic Diseases, X-Linked / complications
  • Genetic Diseases, X-Linked / pathology
  • Genetic Diseases, X-Linked / physiopathology
  • Genetic Diseases, X-Linked / therapy
  • Humans
  • Intellectual Disability / complications
  • Microcephaly / complications
  • Telomere / metabolism

Supplementary concepts

  • Hoyeraal Hreidarsson syndrome