Discordant detection of monosomy 7 by GTG banding and FISH in a patient with Schwachman-Diamond syndrome

Abstract

Schwachman-Diamond Syndrome (SDS) is an inherited illness characterized by exocrine pancreatic insufficiency and by congenital neutropenia. Patients with SDS are at increased risk of developing myelodysplastic syndrome (MDS) and acute myelogenous leukemia (AML). Bone marrow aspiration and biopsy can be used to detect MDS in a presymptomatic state. Monosomy 7 is a poor prognostic sign in MDS and AML, and therefore establishing its presence is important. However, different methods of detection may lead to different results in some patients.

A three month old girl was referred to Rhode Island Hospital in 1988 with failure to thrive. White blood cell count was mildly depressed at 4 × 10⁹ cells/L and pancreatic insufficiency was demonstrated. The diagnosis of SDS was made. In February of 1998, surveillance bone marrow cytogenetic analysis of a suboptimal specimen demonstrated the following karyotype by GTG banding: 45,XX,-C[3]/46,XX[45]/47,XX+C[1]. Fluorescent in Situ Hybridization (FISH) was performed with a chromosome 7 specific alpha-satellite probe (D7Z1). 373 of 376 cells exhibited only one chromosome 7 signal. A further marrow aspiration in August of 1998 showed an essentially normal karyotype by GTG-banding. FISH with the same chromosome 7 probe showed 230 of 250 cells to be monosomic for chromosome 7. A whole chromosome 7 painting probe demonstrated disomy for chromosome 7 in 90 out of 90 cells, but subtle heteromorphism in the centromeric regions of the two copies of chromosome 7 was noted in some cells.

This case demonstrates that FISH can give results discordant with those of other methodologies and should not be used as a stand-alone cytogenetic test. The chromosome 7 variant detected in this patient may or may not be related to MDS. The relationship of the patient's karyotype to SDS is also not known. Thus, further investigation with repeated bone marrow examination in this patient and further characterization of the abnormalities in other SDS patients are warranted.