Review Question - QID 104486

Fanconi anemia is a genetic disorder related to defective DNA repair, which often presents with arm or thumb defects, short stature, and pancytopenia.

Fanconi anemia (FA) is an autosomal recessive (rarely, it can be X-linked) disorder relating to DNA repair. It is associated with numerous congenital defects, including arm abnormalities (hypoplastic radius), thumb abnormalities, and progressive bone marrow failure. Café-au-lait spots may also be seen. The disorder is associated with an increase in certain hematologic malignancies. Clinicians must have a high index of suspicion for diagnosis, as the phenotype can be variable.

Janus and Moerschel discuss FA. Initially, Fanconi anemia presents with a normocytic or macrocytic anemia, as there is some element of reticulocytosis. Over time, however, FA leads to an increased propensity for progenitor stem cells in the bone marrow to undergo apoptosis. Accordingly, there is progressive pancytopenia, with microcytic anemia, and reticulocytopenia. The average age of diagnosis is 8 years old; however, in some cases obvious congenital abnormalities lead to early diagnosis. However, in about a third of cases, there are no obvious physical abnormality, and aplastic anemia will be the first presenting sign.

Kupfer reviews the mechanism of FA. FA cells are hypersensitive to DNA cross-linking agents. This hypersensitivity results in increased chromosomal abnormalities, including many translocations and "radial chromosomes" (see Illustration A). In recent years, advances have been made in treating FA by the use of stem cell transplantation. However, those children who survive into adulthood are frequently affected by solid tumors, such as squamous cell cancers.

Figure A depicts a thumb abnormality (very thin base of attachment of the thumb) that can be seen in FA. Illustration A shows chromosomal abnormalities that can be seen in FA, particularly radial chromosomes, in which multiple chromosomes are radially arrayed. This finding is useful in diagnosing FA. Illustration B depicts a radiograph of a radial abnormality in a patient with FA.

Incorrect Answers:
Answer 1: Diamond-Blackfan pure red cell aplasia is usually diagnosed around age 3 months.
Answer 2: Iron deficiency anemia is the most common cause of anemia but does not have associated thumb defects.
Answer 4: Hemoglobinopathies, like sickle cell disease, are not associated with the thumb findings depicted.
Answer 5: Some infections, such as parvovirus B19, may cause red cell aplastic anemia, but not the other findings depicted in the question stem.