Dyskeratosis congenita ( DC ) is a heterogeneous multi-system syndrome exhibiting marked clinical and genetic heterogeneity. In its classical form it is characterised by mucocutaneous abnormalities, bone marrow failure and a predisposition to cancer.
Bone marrow failure is the principal cause of mortality and patients display features of premature aging.
Studies over the last 15 years have led to significant advances with ten DC genes ( DKC1, TERC, TERT, NOP10, NHP2, TINF2, C16orf57/USB1, TCAB1, CTC1 and RTEL1 ) having been characterized.
Nine of these are important in telomere maintenance.
Dyskeratosis congenita is therefore principally a disease of defective telomere maintenance and patients usually have very short telomeres.
These genetic advances have led to the unification of dyskeratosis congenital with a number of other disorders. This includes the severe multisystem disorders Hoyeraal-Hreidarsson and Revesz syndromes as well as a subset of patients with aplastic anaemia, myelodysplasia, leukaemia, liver disease and idiopathic pulmonary fibrosis.
This wide spectrum of diseases ranging from classical dyskeratosis congenita to aplastic anaemia can be regarded as disorders of defective telomere maintenance, the telomereopathies. ( Xagena )
Dokal I, Human Gene Therapy, 2013