Bone marrow - nonneoplastic
Alterations in cellularity
Dyskeratosis congenita

Author: Dragos Luca, M.D. (see Authors page)

Revised: 7 July 2017, last major update April 2013

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PubMed Search: Bone marrow dyskeratosis congenita [title]

Cite this page: Dyskeratosis congenita. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/bonemarrowdyskeratosiscongenita.html. Accessed July 25th, 2017.
Definition / general
  • Also called Zinsser-Engman-Cole syndrome
  • Rare; 90% males; most patients are diagnosed as adults
  • X linked recessive inheritance most common; autosomal dominant and recessive forms as well as sporadic occurrences also recognized
  • X linked cases are linked to mutations in DKC1 gene encoding dyskerin, a small nucleolar ribonucleoprotein particle, important in ribosomal RNA processing and part of telomerase complex (Int J Hematol 2005;82:184)
  • Autosomal dominant cases are linked to mutations in telomerase RNA gene (TERC) that impair telomerase function, leading to critically short telomeres
  • Severe variant: Hoyeraal-Hreidarsson syndrome, a multisystem disorder with aplastic anemia, immunodeficiency, microcephaly, cerebellar hypoplasia and growth retardation
Diagrams / tables

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Defects in cellular proliferation
and differentiation that give rise
to dyskeratosis congenita

Clinical presentation and diagnosis
  • Clinical triad: cutaneous hyperpigmentation, dystrophic nails, mucosal leukoplakia (may become malignant - squamous cell carcinoma)
  • Causes progressive and ultimately fatal loss of hematopoietic renewal (pancytopenia)
  • Other common physical findings: ocular abnormalities, dental caries, esophageal webs, genitourinary defects, restrictive pulmonary disorder
  • Rarely associated with usual interstitial pneumonia causing death from respiratory failure (Mayo Clin Proc 2005;80:817)
  • Although probably an inherited DNA repair defect disorder (similar to Fanconi anemia), no obviously increased sensitivity to mitomycin C and diepoxybutane
  • Combined flow cytometry and FISH for very short telomeres in peripheral blood lymphocytes may confirm the diagnosis
Case reports
Treatment and prognosis
  • Hematologic support with blood products for various cytopenias
  • Androgens, G-CSF, erythropoietin, bone marrow transplant, hematopoietic stem cell transplant
  • Over two thirds of patients die of bone marrow failure at an early age (20 - 25 years)
  • Longer survival associated with increased risk of carcinomas and myelodysplasia (10 - 15%)
Clinical images

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Reticular skin pigmentation

Reticular pigmentation

Dorsum of tongue

Ulceroproliferative growth

Clinical data of the DKC proband in the first pedigree


Plantar surface of hands

Palmar surface of hands

Hyperpigmentation and dystrophic nails

Epiphora and ectropion

Microscopic (histologic) description
  • Bone marrow morphology very similar to Fanconi anemia (initially normo / hypercellular with megaloblastic changes, eventual aplasia in > 50%, possibly late AML)
Microscopic (histologic) images

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Histopathological features of dyskeratosis congenita

Lymph node: metastatic squamous cell cac

Dorsum of tongue: squamous cell carcinoma

Dorsum of tongue:
richly vascular
with mild chronic
inflammatory infiltrate

Molecular / cytogenetics description
  • X linked form: DKC1 gene on chromosome Xq28 encodes dyskerin thought to be involved in ribosomal assembly but also associated with the RNA template for telomerase (TERC) and possibly involved in telomere maintenance
  • Autosomal dominant form: TERC gene (also known as DKC2) demonstrates "disease anticipation" (earlier onset in successive generations)
  • Autosomal recessive form: unknown genetic association
  • Normal chromosome breakage studies
Differential diagnosis