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Key Features

Essentials of Diagnosis

  • Progressive pancytopenia

  • Macrocytosis

  • Multiple congenital anomalies

  • Increased chromosome breakage in peripheral blood lymphocytes

General Considerations

  • Most common inherited bone marrow failure syndrome; 75–90% of affected individuals develop bone marrow failure in the first 10 years of life

  • Characterized by defective DNA repair that is caused by a variety of genetic mutations

  • Inheritance is autosomal recessive

  • Occurs in all ethnic groups

Clinical Findings

Symptoms and Signs

  • Symptoms are determined principally by the degree of hematologic abnormality

  • Thrombocytopenia may cause purpura, petechiae, and bleeding

  • Neutropenia may cause severe or recurrent infections

  • Anemia may cause weakness, fatigue, and pallor

  • Congenital anomalies are present in at least 50% of patients; most common include

    • Abnormal pigmentation of the skin (generalized hyperpigmentation, café au lait or hypopigmented spots)

    • Short stature with delicate features

    • Skeletal malformations (hypoplasia, anomalies, or absence of the thumb and radius)

  • More subtle anomalies are hypoplasia of the thenar eminence or a weak or absent radial pulse

  • Associated renal anomalies include

    • Aplasia

    • Horseshoe kidney

    • Duplication of the collecting system

  • Other anomalies

    • Microcephaly

    • Microphthalmia

    • Strabismus

    • Ear abnormalities

    • Hypogenitalism

Differential Diagnosis

  • Idiopathic thrombocytopenic purpura (ITP)

  • Other more common causes of thrombocytopenia


Laboratory Findings

  • Thrombocytopenia or leukopenia typically occurs first, followed over the course of months to years by anemia and progression to severe aplastic anemia

  • Macrocytosis

    • Virtually always present

    • Usually associated with anisocytosis and an elevation in fetal hemoglobin levels

  • Bone marrow reveals hypoplasia or aplasia

  • Diagnosis is confirmed by demonstration of an increased number of chromosome breaks and rearrangements in peripheral blood lymphocytes

    • Use of diepoxybutane to stimulate these breaks and rearrangements provides a sensitive assay that is virtually always positive in children with Fanconi anemia, even before the onset of hematologic abnormalities

  • Specific Fanconi genes (FANCA, B, C, and others) have been identified and transmission is generally autosomal, although FANCB is on the X chromosome


  • Attentive supportive care is critical

  • Parenteral broad-spectrum antibiotics are required for patients with neutropenia in whom fever develops

  • Transfusions

    • Should be used judiciously, especially in the management of thrombocytopenia, which frequently becomes refractory to platelet transfusions as a consequence of alloimmunization

    • Transfusions from family members should be discouraged because of the negative effect on the outcome of bone marrow transplant

  • Oxymetholone

    • At least 50% of patients respond, albeit incompletely

    • Many experts recommend institution of androgen therapy before transfusions are needed

    • Side effects associated with therapy include hepatotoxicity, hepatic adenomas, and masculinization

  • Reduced intensity hematopoietic stem cell transplant

    • Definitive treatment

    • Ideally, should come from an HLA-identical sibling donor

    • Although matched unrelated and cord transplant may be considered




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