Bone marrow nonneoplastic
Alterations in cellularity
Dyskeratosis congenita
Author: Dragos C. Luca, M.D.
Last author update: 1 April 2013
Last staff update: 22 July 2019
Copyright: 2002-2019, PathologyOutlines.com, Inc.
PubMed Search: Bone marrow dyskeratosis congenita [title]
Table of Contents
Definition / general | Diagrams / tables | Clinical presentation and diagnosis | Case reports | Treatment and prognosis | Clinical images | Microscopic (histologic) description | Microscopic (histologic) images | Molecular / cytogenetics description | Differential diagnosis | Additional referencesCite this page: Luca DC. Dyskeratosis congenita. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/bonemarrowdyskeratosiscongenita.html. Accessed November 27th, 2024.
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
Images hosted on other servers:
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
- Infant with severe variant of X linked disease (Hoyeraal-Hreidarsson syndrome) and enterocolitis (J Pediatr Gastroenterol Nutr 2009;49:359)
- 38 year old man with dyskeratosis congenita with malignant transformation (BMJ Case Rep 2011 Jan 11;2011)
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
Images hosted on other servers:
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
Images hosted on other servers:
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
Additional references
- Foucar: Bone Marrow Pathology, 2nd edition, 2001, Foucar: Bone Marrow Pathology, 3rd edition, 2011, Foucar: Non-Neoplastic Disorders of Bone Marrow (Atlas of Non-Tumor Pathology), 1st edition, 2009, Penchansky: Pediatric Bone Marrow, 2004, eMedicine: Dyskeratosis Congenita, OMIM: Dyskeratosis Congenita, X-linked; DKCX, OMIM: Dyskeratosis Congenita, Autosomal Dominant 1; DKCA1, OMIM: Dyskeratosis Congenita, Autosomal Recessive 1; DKCB1
