Dyskeratosis congenita (DKC)

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Written2001-08Claude Viguié
Service de Dermatologie, Hôpital Tarnier-Cochin, 89 rue d'Assas, 75006 Paris, France

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1. Identity

Other namesZinsser Cole Engeman syndrome
Hoyeraal Hreidarsson syndrome
Atlas_Id 10034
Genes implicated inDKC1  NHP2  NOP10  PARN  RTEL1  TERC  TERT  TINF2  WRAP53 
Note Hoyeraal Hreidarsson syndrome is a more severe variant
Inheritance X-linked recessive form constitute more than 80% of cases and 91% of DKC patients are males

2. Clinics

Note The disease is characterised by a multisystem failure, affecting essentially tissues with a high proliferation rate: skin, mucous membranes, bone marrow
Phenotype and clinics
  • Short stature (16%)
  • Cutaneous signs:
    Hyperpigmentation, telangiectasia, atrophy (poïkilodermia)
    Dystrophic nails and palmoplantar keratoderma , hyperhidrosis
    Mucosal leucoplakia
    Dental caries or loss ( 18%)
    Blepharitis, conjunctivitis, epiphora (36%)
    Sparse eyebrows / eyelashes
    Alopecia (16%)
    Urethral stricture, phimosis (7%)
  • Bone marrow failure, peripheral pancytopenia ( 93%)
  • Others signs:
    Oesophageal stricture (14%)
    Pulmonary fibrosis (19%)
    Liver cirrhosis (5%)
    Hypogonadism (8%)
    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 myelodysplasia.
  • The mucosal leucoplakia can transform into spinocellular carcinoma.
  • Other carcinomas can develop during the third decade of life: lung, colon, larynx, oesophagus, pancreas, Hodgkin disease.
  • 3. Cytogenetics

    Inborn conditions 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.

    4. Genes involved and Proteins

    Gene NameDKC1 (dyskeratosis congenita 1, dyskerin)
    Location Xq28
    Description DKC1 encodes for Dyskerin, a 514 aminoacid protein
    Expression widespread tissue repartition
    Function 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.

    5. Bibliography

    X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.
    Knight SW, Heiss NS, Vulliamy TJ, Greschner S, Stavrides G, Pai GS, Lestringant G, Varma N, Mason PJ, Dokal I, Poustka A
    American journal of human genetics. 1999 ; 65 (1) : 50-58.
    PMID 10364516
    Dyskeratosis congenita, telomeres and human ageing.
    Marciniak RA, Johnson FB, Guarente L
    Trends in genetics : TIG. 2000 ; 16 (5) : 193-195.
    PMID 10782108
    Dyskeratosis congenita: new clinical and molecular insights into ribosome function.
    McGrath JA
    Lancet. 1999 ; 353 (9160) : 1204-1205.
    PMID 10217077
    A telomerase component is defective in the human disease dyskeratosis congenita.
    Mitchell JR, Wood E, Collins K
    Nature. 1999 ; 402 (6761) : 551-555.
    PMID 10591218
    Mutant dyskerin ends relationship with telomerase.
    Shay JW, Wright WE
    Science (New York, N.Y.). 1999 ; 286 (5448) : 2284-2285.
    PMID 10636790
    Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita.
    Vulliamy TJ, Knight SW, Mason PJ, Dokal I
    Blood cells, molecules & diseases. 2001 ; 27 (2) : 353-357.
    PMID 11259155

    6. Citation

    This paper should be referenced as such :
    Viguié, C
    Dyskeratosis congenita (DKC)
    Atlas Genet Cytogenet Oncol Haematol. 2001;5(4):308-310.
    Free journal version : [ pdf ]   [ DOI ]
    On line version : http://atlasgeneticsoncology.usal.es/classic/Tumors/DyskeratosID10034.html

    7. External links

    OrphanetDyskeratosis congenita
    REVIEW articlesautomatic search in PubMed
    Last year articlesautomatic search in PubMed

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