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Dyskeratosis Congenita (DC) is an inherited bone marrow failure syndrome exhibiting considerable clinical and genetic heterogeneity.
The disease was first described by Zinsser in 1906 and was recognized as a clinical entity by Engman (1926) and Cole (1930). The classic and initial form is usually characterized by the mucocutaneous triad of nail dystrophy, oral leukoplakia and reticular pigmentation of the skin. Thereafter, new cases were identified and showed that DC could affect multiple systems of the body, particularly the bone marrow (BM). 80% of patients develop bone marrow failure (BMF) by age 30 years. Pulmonary fibrosis and cancer are severe complications during the evolution of the disease.
A variety of other somatic abnormalities are often present, which may involve the eye epithelia, neurological, pulmonary, skeletal, dental and gastrointestinal systems, hair loss or greying, and the genitourinary tract [1-3].
The phenotype characteristics of DC are variable even between family members with the same mutation and they can present differences in the penetrance, severity, and development of clinical features.
The disease was predominantly thought of as being X-linked recessive (OMIM 305000), caused by a missense mutation in DKC1 gene. This gene encodes a nucleolar protein (dyskerin) that is involved in ribosome biogenesis and telomere maintenance. Autosomal dominant (AD) and autosomal recessive (AR) forms of DC are now recognized (OMIM 127550; 224230; 268130; 613987; 613988; 613989; 613990; 615190; 616353; 616553). The disease is a result of short telomeres and mutations in 10 genes associated with telomerase and telomere components. However, the genetic basis of the disease is still undetectable in nearly 40% of DC cases [2, 4].
Since its initial description, the group of diseases referred to by the term “dyskeratosis congenita” has expanded considerably. It has become popular to refer to them as the “telomereopathies” or “short telomere syndromes”.
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