As chromosomal instability may contribute to leukemogenesis in patients with 
congenital bone marrow failure (CBMF) disorders, it was the aim of this study to 
characterize chromosomally aberrant clones that arise during the clinical course 
of disease by means of R-banding and fluorescence in situ hybridization (FISH) 
analyses. In addition, multicolor-FISH and array-comparative genomic 
hybridization (CGH) were applied to characterize clonal chromosome aberrations 
in more detail. Between January 2004 and December 2005, we prospectively 
analyzed 90 samples of 73 patients with proven or suspected CBMF disorders 
enrolled in a German Study Network of CBMF diseases. Clonal aberrations could be 
identified in four of 73 patients examined. In one child with congenital 
thrombocytopenia, Jacobsen syndrome [del(11)(q24)c] was diagnosed, and thus a 
CBMF could be excluded. In a girl with Shwachman-Diamond syndrome, two 
independent clones, one with an isochromosome i(7)(q10), another with a complex 
aberrant karyotype, were identified. Simultaneously, transition into a 
myelodysplastic syndrome (MDS) occurred. The brother, who was also afflicted 
with Shwachman-Diamond syndrome, showed an isochromosome i(7q) as a single 
aberration. In the fourth patient with severe congenital neutropenia, an 
add(21)(q22) marker containing a low-level amplification of the AML1 gene was 
identified at the time point of transition into acute myelogenous leukemia 
(AML). In summary, we suggest that follow-up of patients with CBMF using 
chromosome and FISH analyses will be helpful for the early detection of 
transition into MDS or AML and thus should be an integral part of the clinical 
management of these patients.