Bone marrow nonneoplastic

Alterations in cellularity

Fanconi anemia

Last author update: 1 March 2013
Last staff update: 22 July 2019

Copyright: 2002-2019,, Inc.

PubMed Search: Bone marrow [title] Fanconi anemia [title]

Dragos C. Luca, M.D.
Page views in 2022: 1,633
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Cite this page: Luca DC. Fanconi anemia. website. Accessed June 1st, 2023.
Definition / general
  • Originally described in 1927 by Guido Fanconi, who reported 3 brothers with pancytopenia and multiple physical abnormalities (eMedicine: Fanconi Anemia)
  • Most common inherited bone marrow failure syndrome; incidence at birth of 1 per 100 - 350K live births (Wikipedia: Fanconi Anemia)
  • Typically autosomal recessive with intellectual disability and multiple bone, skin and renal abnormalities
  • Associated with MDS / AML (15 - 20% of patients), hepatocellular adenoma
  • Presence of significant birth defects correlates with early onset hematologic disease / anemia
  • Note: Fanconi syndrome is a generalized dysfunction of proximal renal tubule transport with no primary glomerular involvement
Diagrams / tables

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Diagnostic algorithm

Clinical features and diagnosis
  • Usually diagnosed in infancy; 10% diagnosed at age 16 years or older; rarely diagnosed in 40's or 50's
  • Prenatal diagnosis is possible by chromosome breakage analysis of chorionic villus, amniocentesis or cord blood lymphocyte samples
  • Highly variable clinical features with occasional patients that are phenotypically normal (up to 30% according to some studies)
  • Progressive lethal anemia associated with brown skin pigmentation, hypoplastic bone marrow, renal hypoplasia, absent or hypoplastic thumbs or radii, short stature and other anomalies; some patients have milder phenotype
  • Thrombocytopenia: often the first evidence of impending hematopoietic failure
  • Variable pancytopenia, macrocytosis, increased fetal hemoglobin and I antigen expression on erythrocytes (evidence of "stressed" erythropoiesis)
  • Stimulated peripheral lymphocyte cultures: characteristic pattern of combined G2 phase prolongation and arrested G2 phase, detectable by flow cytometry
Case reports
Treatment and prognosis
  • 50% improve with androgens; also G-CSF; stem cell transplantation
  • Late development of myelodysplasia or AML in approximately 15 - 20% of patients
  • Median survival is 7 years
Clinical images

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Clinodactyly with brachymesophalangia

Microscopic (histologic) description
  • Early bone marrow specimens may be normocellular with megaloblastic features but gradual aplasia develops with severe pancytopenia by mid to late childhood
  • Late stages: decreased / absent megakaryocytes, marked hypocellularity, rare small foci of erythropoiesis / myelopoiesis, fatty replacement
  • Rare patients present directly with AML
Microscopic (histologic) images

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Hypocellular spicule with fatty infiltration

Cytology images

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Aspirate smear findings

Molecular / cytogenetics description
  • At the molecular level, 8 different genetic types of FA complementary groups have been described
  • Several genes involved: FAC (9q22.3), FAA (16q24.3), FAG (19p13)
  • Chromosomal instability due to increased number of chromosomal breaks, gaps, rearrangements and endoreduplication (OMIM: Fanconi Anemia, Complementation Group A; FANCA)
  • 12 mutated genes identified to date; proteins are involved in repair of DNA damage
  • Unique cytogenetic finding is increased sensitivity to apoptosis inducing effects of mitomycin C and diepoxybutane
Molecular / cytogenetics images

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Chromosome breakage test

Representative karyotypes

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