Cancer prone diseases
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Dyskeratosis congenita (DKC)
Dyskeratosis congenita (DKC)
Zinsser Cole Engeman syndrome , Hoyeraal Hreidarsson syndrome
Hoyeraal Hreidarsson syndrome is a more severe variant
X-linked recessive form constitute more than 80% of cases and 91% of DKC patients are males
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1775 Dyskeratosis congenita
Phenotype and clinics
Short stature (16%)
Hyperpigmentation, telangiectasia, atrophy (poïkilodermia)
Dystrophic nails and palmoplantar keratoderma , hyperhidrosis
Dental caries or loss ( 18%)
Blepharitis, conjunctivitis, epiphora (36%)
Sparse eyebrows \/ eyelashes
Urethral stricture, phimosis (7%)
Bone marrow failure, peripheral pancytopenia ( 93%)
Oesophageal stricture (14%)
Pulmonary fibrosis (19%)
Liver cirrhosis (5%)
Abnormal bone trabeculation, osteoporosis (4%)
Immune abnormalities: reduced or increased immunoglobulin level, T- and\/or B-lymphocyte deficiency.
Mild Mental Retardation, learning difficulties (21%)
leucokeratosis of the tongue, poïkilodermia of the foot and the trunk, onychopathy. Courtesy Daniel Wallach
The major part of patients di before 20 years, mainly from infectious complications of immune deficiency.
90% of patients have haematological abnormalities when 30 year-old , and bone marrow failure is the main cause of early morbidity in 71% of cases. It can evolve toward aplastic anemia or
The mucosal leucoplakia can transform into spinocellular carcinoma.
Other carcinomas can develop during the third decade of life: lung, colon, larynx, oesophagus, pancreas,
An excess of chromosome breakages has been reported in DKC but this finding is controversial; not frequently, rearrangements comparable to what is observed in Fanconi anemia are described: chromosome instability and breakage (di- and tricentric chromosomes), either spontaneous or induced by clastogenic agents (mitomycin C). Cells with a high turn-over (skin fibroblasts, lymphocytes, bone marrow cells, digestive tract) would be particularly sensitive to chromosome rearrangements and DNA damage.
Genes involved and Proteins
DKC1 encodes for Dyskerin, a 514 aminoacid protein
widespread tissue repartition
Dyskerin is the nucleolar pseudouridine synthetase component of the box H+ACA snoRNAs. It also interacts with the RNA component of human telomerase. Chromosome instability could be linked to increased telomere shortening due to an alteration in telomerase-dependant telomere maintenance. DKC1 plays a role in ribosomal RNA synthesis and in ribosome biogenesis; DKC is a human ribosomopathy.
To be noted
X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.
Knight SW et al
Dyskeratosis congenita, telomeres and human ageing.
Marciniak RA et al
Dyskeratosis congenita: new clinical and molecular insights into ribosome function.
McGrath JA et al
A telomerase component is defective in the human disease dyskeratosis congenita.
Mitchell JR et al
Mutant dyskerin ends relationship with telomerase.
Shay JW et al
Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita.
Vulliamy TJ et al
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