Dyskeratosis congenita (DKC)

2001-08-01   Claude Viguié  

Identity

Name

Dyskeratosis congenita (DKC)

Alias

Zinsser Cole Engeman syndrome , Hoyeraal Hreidarsson syndrome

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

Omim

127550 , 224230 , 305000 , 613987 , 613988 , 613989 , 613990 , 615190 , 616353

Mesh

D019871

Orphanet

1775 Dyskeratosis congenita

Umls

C0265965

Clinics

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%)
    • Atlas Image
    leucokeratosis of the tongue, poïkilodermia of the foot and the trunk, onychopathy. Courtesy Daniel Wallach

    Prognosis

  • 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.

    • Cytogenetics

    Inborn condition

    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

    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.

    To be noted

    Hgmd

    119096

    Article Bibliography

    Pubmed IDLast YearTitleAuthors
    103645161999X-linked dyskeratosis congenita is predominantly caused by missense mutations in the DKC1 gene.Knight SW et al
    107821082000Dyskeratosis congenita, telomeres and human ageing.Marciniak RA et al
    102170771999Dyskeratosis congenita: new clinical and molecular insights into ribosome function.McGrath JA et al
    105912181999A telomerase component is defective in the human disease dyskeratosis congenita.Mitchell JR et al
    106367901999Mutant dyskerin ends relationship with telomerase.Shay JW et al
    112591552001Very short telomeres in the peripheral blood of patients with X-linked and autosomal dyskeratosis congenita.Vulliamy TJ et al