Fanconi anemia overview

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Shyam Patel [2]

Overview

Fanconi anemia (FA) is a genetic disease that affects children and adults from all ethnic backgrounds.[1] The disease is named after the Swiss pediatrician who originally described this disorder, Guido Fanconi. FA is characterized by short stature, skeletal anomalies, increased incidence of solid tumors and leukemias, bone marrow failure (aplastic anemia), and cellular sensitivity to DNA damaging agents such as mitomycin C.

Historical perspective

The discovery of Fanconi anemia is largely the work of the Swiss pediatrician Guido Fanconi who observed various findings of the disease to be different than pernicious anemia. Over the coming decades, multiple advances in diagnostics have been made by various groups. Bone marrow transplant was optimized for Fanconi anemia in the 1980s. Most recently, in the 2010s, various new genomic alterations have been associated with Fanconi anemia.

Classification

Fanconi anemia is currently classified by complementation group.

Pathophysiology

In order to understand the pathophysiology, it is important to understand normal physiology of DNA repair. There are eight FANC family members that are activated during times of DNA damage. These proteins function in repairing damaged genetic material. In patients with Fanconi anemia, there is impaired DNA damage response due to mutations in the FANC family genes, and this leads to chromosomal instability and susceptibility to cross-linking agents. These cross-linking agents can lead to the generation of reactive oxygen species.

Causes

Fanconi anemia an autosomal recessive genetic disorder that is caused by mutations in various genes of the FANC family.

Differentiating Fanconi anemia from other diseases

Fanconi anemia must be differentiated from aplastic anemia, paroxysmal nocturnal hemoglobinuria, chromosomal breakage syndromes, and hereditary bone marrow failure syndromes (dyskeratosis congenita and other short telomere syndromes). Each disease has a different pathophysiology, exam findings, and histopathology.

Epidemiology and demographics

Fanconi anemia is rare overall, but it is one of the most common inherited bone marrow failure syndromes. It is typically diagnosed in children with a median age of diagnosis of 7.6 years. There is no racial predilection for Fanconi anemia. It is slightly more common in males than females with a ratio of 1.2:1.

Risk factors

The major risk factor for Fanconi anemia is genetic inheritance. It is inherited in an autosomal recessive pattern.

Screening

There are no recommendations on screening for Fanconi anemia.

Natural History, Complications and Prognosis

Diagnosis

History and Symptoms

Physical Examination

  • Congenital malformations are the most common presenting features of FA.
  • Patients with FA usually present with hypo/hyperpigmentation, café-au-lait spots, short staure and thumb or other radial abnormalities.
  • Vital Signs Usually normal sometime patients present with fever due to superimposed infection.
  • Skin abnormalities in Fanconi anemia can include generalized hyperpigmentation on the trunk, neck, and intertriginous areas, the aforementioned café au lait spots, and hypopigmented areas. Delicate features can also be characteristic of patients.

Laboratory Findings

Electrocardiogram

X-ray

CT

MRI

Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

References

  1. Krausz C, Riera-Escamilla A, Chianese C, Moreno-Mendoza D, Ars E, Rajmil O; et al. (2018). "From exome analysis in idiopathic azoospermia to the identification of a high-risk subgroup for occult Fanconi anemia". Genet Med. doi:10.1038/s41436-018-0037-1. PMID 29904161.