Diagnostic Overlap between Fanconi Anemia and the Cohesinopathies : Roberts Syndrome and Warsaw Breakage Syndrome

Abstract EN

Fanconi anemia (FA) is a recessively inherited disease characterized by multiple symptoms including growth retardation, skeletal abnormalities, and bone marrow failure.

The FA diagnosis is complicated due to the fact that the clinical manifestations are both diverse and variable.

A chromosomal breakage test using a DNA cross-linking agent, in which cells from an FA patient typically exhibit an extraordinarily sensitive response, has been considered the gold standard for the ultimate diagnosis of FA.

In the majority of FA patients the test results are unambiguous, although in some cases the presence of hematopoietic mosaicism may complicate interpretation of the data.

However, some diagnostic overlap with other syndromes has previously been noted in cases with Nijmegen breakage syndrome.

Here we present results showing that misdiagnosis may also occur with patients suffering from two of the three currently known cohesinopathies, that is, Roberts syndrome (RBS) and Warsaw breakage syndrome (WABS).

This complication may be avoided by scoring metaphase chromosomes—in addition to chromosomal breakage—for spontaneously occurring premature centromere division, which is characteristic for RBS and WABS, but not for FA.